{"id":1356,"date":"2023-01-05T00:07:29","date_gmt":"2023-01-05T00:07:29","guid":{"rendered":"https:\/\/mpsdsehcp-dev-001.azurewebsites.net\/en\/mucopolysaccharidosis-mps\/?page_id=1356"},"modified":"2023-12-04T09:16:17","modified_gmt":"2023-12-04T09:16:17","slug":"types-of-mps","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-gb\/mps\/types-of-mps\/","title":{"rendered":"Types of MPS"},"content":{"rendered":"<div id=\"acf-block-63fcf7770ed59\" class=\"hero hero-no-overlay hero-large-first-para\">\n            <div class=\"hero-background-image hero-background-image-desktop\" style=\"background-image: url(https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/MPS-VI-Oli-2000x423.jpg);\"><\/div>\n\t    <div class=\"hero-background-image hero-background-image-mobile\" style=\"background-image: url(https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/12\/Blue.jpg?v=0.24);\"><\/div>\n    \t<div class=\"overlay\"><\/div>\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"hero-content\">\n\t\t\t    \t\t\t\t\t\t\t\t\t\t\t\t    <h1>Types of MPS\n<\/h1>\n\t\t\t\t\t\t\t\t\t\t\t\t    <p>Multisystemic, unpredictable and life threatening<\/p>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n\n<div id=\"Variability-in-progression\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770edff\" class=\"block-wysiwyg\">\n            <h2>Variability in disease progression and presentation often delays diagnosis, making early intervention critical<sup>1<\/sup><\/h2>\n<p>While each subtype of MPS disorder is clinically distinct, all feature the life-limiting, progressive, multisystemic disease manifestations common to MPS disease pathology.<sup>2,3,4,5<\/sup> Management of patients with MPS requires an understanding of the specific clinical manifestations and management recommendations for each MPS subtype.<sup>2,6<\/sup><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"MPS-I\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770ee3b\" class=\"block-wysiwyg\">\n            <h2>MPS I<\/h2>\n<p>Disease name: <strong>Hurler, Hurler\/Scheie, Scheie<\/strong> | Deficient enzyme: <strong>\u03b1-L-iduronidase<\/strong> | Gene symbol:<strong> <em>IDUA<\/em><\/strong><\/p>\n<h3>Patients with Mucopolysaccharidosis Type I (MPS I) are at increased risk for severe morbidity and early mortality<sup>1<\/sup><\/h3>\n<p>MPS I is a progressive condition<sup>2<\/sup> that has been divided into 3 subtypes known as Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H\/S), and Scheie syndrome (MPS I-S).<sup>3<\/sup> All subtypes of MPS I are caused by a deficiency of the enzyme \u03b1-L-iduronidase, which is required for the degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate,<sup>2,4<\/sup> with resulting progressive, multisystemic manifestations.<sup>2<\/sup><\/p>\n<ul>\n<li>MPS I-H typically presents within the first 2 years of life with developmental delay, cognitive decline and rapid progression<sup>1,2<\/sup><\/li>\n<li>MPS I-H\/S typically presents between the ages of 3 and 7 with mild or absent cognitive decline and slower progression<sup>1,2<\/sup><\/li>\n<li>MPS I-S typically presents between the ages of 5 and 13 with no cognitive decline and slower progression<sup>1,2<\/sup><\/li>\n<\/ul>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770eed2\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Observed presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Symptoms appear at varying ages depending on the specific enzyme deficiency and rate of disease progression:<sup>1<\/sup>\n<ul class=\"sub_page-child\">\n<li>H, ages 0 to 2<\/li>\n<li>H\/S, ages 3 to 7<\/li>\n<li>S, ages 5 to 13<\/li>\n<\/ul>\n<\/li>\n<li>Observed presentation includes:<sup>5<\/sup>\n<ul class=\"sub_page-child\">\n<li>Change in facial features<\/li>\n<li>Restricted joint movement<\/li>\n<li>Skeletal deformity<\/li>\n<li>Macrocephaly<\/li>\n<li>Frequent respiratory infections<\/li>\n<li>Cardiomyopathy<\/li>\n<li>Recurrent ear infections<\/li>\n<li>Hernias<\/li>\n<li>Kyphosis\/gibbus deformity<\/li>\n<\/ul>\n<\/li>\n<li>Specific recommendations for consideration of MPS I include:<sup>6<\/sup>\n<ul class=\"sub_page-child\">\n<li>Children with gibbus deformity, enlarged tongue, and\/or 2 or more surgeries before 18 months should prompt diagnostic testing<\/li>\n<li>Children over 2 years of age with claw hands, cardiac problems and\/or 2 or more surgeries before age 10 should prompt diagnostic testing<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Overall disease burden:\n<ul class=\"sub_page-child\">\n<li>Patients experience multiorgan dysfunction and have a high disease burden<sup>1<\/sup><\/li>\n<li>This progressive, debilitating disease also puts psychological and financial burdens on patients and their families<sup>5<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Hurler (H):\n<ul class=\"sub_page-child\">\n<li>Symptoms appear shortly after birth, progress rapidly, and typically include:<sup>1<\/sup>\n<ul class=\"sub_page-child\">\n<li>Developmental delay and cognitive decline<\/li>\n<li>Coarse facial features<\/li>\n<li>Joint stiffness and contractures<\/li>\n<li>Short stature<\/li>\n<li>Hepatosplenomegaly<\/li>\n<li>Respiratory and cardiac disease<\/li>\n<\/ul>\n<\/li>\n<li>Left untreated, patients typically die within the first decade of life, often due to cardiorespiratory failure and neurological disease<sup>1,5<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Hurler-Scheie (H\/S) and Scheie (S):\n<ul class=\"sub_page-child\">\n<li>Symptom presentation varies according to age<sup>7<\/sup>:\n<ul>\n<li>Hernia typically occurs before age 5<\/li>\n<li>Joint contractures and dysostosis multiplex typically arise between the ages of 5 and 12<\/li>\n<li>Scoliosis, carpal tunnel syndrome, and congestive heart failure often occur in adolescence<\/li>\n<li>Glaucoma, cardiomyopathy, and myelopathy typically arise in early adulthood<\/li>\n<\/ul>\n<\/li>\n<li>Left untreated, patients with MPS I-H\/S typically die within the second or third decade of life<sup>1<\/sup><\/li>\n<li>Left untreated, patients with MPS I-S usually sustain significant morbidity<sup>1<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Patients with MPS I have a high surgical burden, which may include:<sup>6<\/sup>\n<ul class=\"sub_page-child\">\n<li>Myringotomies<\/li>\n<li>Hernia surgery, often with repeat procedures<\/li>\n<li>Adenoidectomy<\/li>\n<li>Tonsillectomy<\/li>\n<li>Ventriculoperitoneal shunt<\/li>\n<li>Spinal procedures<\/li>\n<li>Carpal tunnel surgery<\/li>\n<li>Orthopaedic surgeries of hip, knee and foot<\/li>\n<\/ul>\n<\/li>\n<li>Because patients with MPS I often experience anaesthetic complications due to obstructed airways, special care must be taken when undergoing surgery<sup>8<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>MPS I is caused by pathogenic variants in the \u03b1-L-iduronidase gene, <em>IDUA<\/em><sup>4<\/sup><\/li>\n<li>There are over 100 known pathogenic variants within <em>IDUA<\/em><sup>9<\/sup><\/li>\n<li>These pathogenic variants lead to accumulation of the GAGs heparan and dermatan sulphate<sup>4<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>The potential use of enzyme replacement therapy and hematopoietic stem cell transplantation (HSCT) are both important considerations in the management of MPS I:<sup>1,5<\/sup><\/li>\n<li>Patients with the Hurler phenotype diagnosed before 2.5 years should be treated with HSCT<sup>10<\/sup><\/li>\n<li>All other patients should be treated with enzyme replacement therapy.<sup>10<\/sup><\/li>\n<li>Available treatment guidelines include:\n<ul class=\"sub_page-child\">\n<li>Martins AM <em>et al<\/em>. Guidelines for the management of mucopolysaccharidosis type I. <em>J Pediatr<\/em> 2009;155(4)(suppl 2):S32\u2013S46.<\/li>\n<li>Muenzer J <em>et al<\/em>.\u00a0International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. <em>Pediatrics <\/em>2009;123(1):19\u201329.<\/li>\n<li>de Ru MH <em>et al<\/em>. Enzyme replacement therapy and\/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure.<em> Orphanet J Rare Dis<\/em> 2011;6(55):1\u20139.<\/li>\n<li>Langereis EJ <em>et al<\/em>. Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure. <em>Orphanet J Rare Dis<\/em> 2013;8(155):1\u201316.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1. Beck M <em>et al<\/em>. The natural history of MPS I: global perspectives from the MPS I Registry. <em>Genet Med<\/em>.2014;16(10):759\u2013765.<br \/>\n2. Clarke LA <em>et al<\/em>. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. <em>Pediatrics<\/em> 2009;132(1):229\u2013240.<br \/>\n3. Yasuda E <em>et al<\/em>. Long-term follow-up of post hematopoietic stem cell transplantation for Hurler syndrome: clinical, biochemical, and pathological improvements. <em>Mol Genet Metab Rep<\/em> 2015;2:65\u201376.<br \/>\n4. Shapiro EG <em>et al<\/em>. Neurocognition across the spectrum of mucopolysaccharidosis type I: age, severity, and treatment. <em>Mol Genet Metab<\/em> 2015;116(1-2):61\u201368.<br \/>\n5. Muenzer J <em>et al<\/em>. International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. <em>Pediatrics<\/em> 2009;123(1):19\u201329.<br \/>\n6. Arn P <em>et al<\/em>. Characterization of surgical procedures in patients with mucopolysaccharidosis type I: findings from the MPS I Registry. <em>J Pediatr<\/em> 2009;154(6):859\u2013864.e3.<br \/>\n7. Thomas JA <em>et al<\/em>. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. <em>J Inherit Metab Dis<\/em> 2010;33(4):421\u2013427.<br \/>\n8. Semenza GL <em>et al<\/em>. Respiratory complications of mucopolysaccharide storage disorders. <em>Medicine<\/em> 1988;67(4):209\u2013219.<br \/>\n9. Clarke LA <em>et al<\/em>. Mucopolysaccharidosis type I. In: Pagon RA et al eds. <em>GeneReviews\u00ae<\/em> Seattle, WA: University of Washington, Seattle; 2002. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1162\/?report=reader. Accessed June, 2023.<br \/>\n10. de Ru MH <em>et al<\/em>. Enzyme replacement therapy and\/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. <em>Orphanet J Rare Dis<\/em>. 2011;6(55):1\u20139.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"MPS-II\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770ef4d\" class=\"block-wysiwyg\">\n            <h2>MPS II<\/h2>\n<p>Disease name:<strong> Hunter<\/strong> | Deficient enzyme:<strong> Iduronate 2-sulphatase<\/strong> | Gene symbol: <em><strong>IDS<\/strong><\/em><\/p>\n<h3>Patients with Mucopolysaccharidosis Type II (MPS II) are at elevated risk for severe morbidity and early mortality<sup>16<\/sup><\/h3>\n<p>MPS II, also known as Hunter syndrome, is caused by a genetic pathogenic variant in the iduronate 2-sulphatase (<em>IDS<\/em>) gene leading to deficient cleavage of glycosaminoglycans (GAGs), heparan and dermatan sulphate, which leads to intracellular progressive GAG accumulation with resulting progressive, multisystemic disease.<sup>1,2<\/sup><\/p>\n<ul>\n<li>The rapidly progressing form of MPS II typically presents between 18 and 36 months of age with cognitive dysfunction and severe somatic changes<sup>1,2<\/sup><\/li>\n<li>The slowly progressing form of MPS II typically presents between the ages of 4 and 8 years with no cognitive decline and mild somatic changes<sup>1,2<\/sup><\/li>\n<\/ul>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770efd1\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Observed presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Symptoms appear at varying ages<sup>2<\/sup><\/li>\n<li>Observed presentation includes the following:<sup>3<\/sup>\n<ul>\n<li>Change of facial features<\/li>\n<li>Enlarged tongue<\/li>\n<li>Macrocephaly<\/li>\n<li>Hypertrophic tonsils and adenoids<\/li>\n<li>Irregularly shaped teeth<\/li>\n<li>Recurrent ear infections<\/li>\n<li>Hernias<\/li>\n<li>Pebbled skin<\/li>\n<li>Short stature<\/li>\n<li>Joint contractures<\/li>\n<li>Changes to musculoskeletal system, eyes, gastrointestinal tract, airways and cardiovascular system<\/li>\n<\/ul>\n<\/li>\n<li>Combinations of the above clinical manifestations should prompt testing for MPS II<sup>3<\/sup><\/li>\n<li>There is a high prevalence of MPS II in the Ashkenazi Jewish population<sup>4<\/sup><\/li>\n<li>MPS II is an X-linked recessive disorder, therefore mainly affecting males<sup>2<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Overall disease burden:\n<ul>\n<li>Patients with the rapidly progressing form of disease experience multiorgan dysfunction, resulting in high disease burden<sup>2<\/sup><\/li>\n<li>Patients with the slowly progressing form of disease may present with symptoms and complications that lead to significant morbidity and disability<sup>2<\/sup><\/li>\n<li>Both forms of the disease are associated with severe psychological and financial burdens for patients and their families<sup>3,5<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Rapidly progressing MPS II:\n<ul class=\"sub_page-child\">\n<li>Symptoms may include: <sup>1,2<\/sup>\n<ul class=\"sub_page-child\">\n<li>Cognitive decline with hyperactive and aggressive behaviour<\/li>\n<li>Hernia<\/li>\n<li>Significant multisystemic complications, including skeletal deformities that can restrict pulmonary function <sup>2,5<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Left untreated, patients typically die before 15 years of age; mortality is often associated with cardiorespiratory failure and neurological deterioration. <sup>1,2<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Slowly progressing MPS II:\n<ul>\n<li>Symptoms appear between 4 and 8 years of age with variable progression and typically include:<sup>2<\/sup>\n<ul>\n<li>Short stature<\/li>\n<li>Coarse facial features<\/li>\n<li>Joint contractures<\/li>\n<li>Hernia due to hepatosplenomegaly<\/li>\n<\/ul>\n<\/li>\n<li>Left untreated, patients typically die between the ages of 20 and 60 years of age; mortality is often associated with cardiorespiratory failure. <sup>1,2<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Patients with MPS II typically have a high surgical burden that may include:<sup>2,3<\/sup>\n<ul>\n<li>Myringotomies<\/li>\n<li>Hernia surgery, often with repeat procedures<\/li>\n<li>Adenoidectomy<\/li>\n<li>Tonsillectomy<\/li>\n<li>Cervical decompression<\/li>\n<li>Carpal tunnel surgery<\/li>\n<li>Cardiac valve replacement therapy<\/li>\n<li>Hip and knee replacement and correction of lower limb axis<\/li>\n<\/ul>\n<\/li>\n<li>Patients with MPS II often experience anaesthetic complications due to obstructed airways; therefore, care must be taken for patients undergoing surgery<sup>2,3<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>MPS II is caused by pathogenic variants in the <em>IDS<\/em> gene<sup>1,2<\/sup><\/li>\n<li>There are over 300 known pathogenic variants in the <em>IDS<\/em> gene<sup>6<\/sup><\/li>\n<li>These pathogenic variants, and resulting protein dysfunction, lead to accumulation of the GAGs heparan and dermatan sulphate<sup>1,2<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Enzyme replacement therapy is an important consideration in the management of MPS II<sup>2,3<\/sup><\/li>\n<li>Depending on the severity, neurological manifestations are heterogeneous and require their own specific interventions and management<sup>2,3<\/sup><\/li>\n<li>Available treatment and management recommendations:\n<ul>\n<li>Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. <em>Eur J Pediatr<\/em> 2012; 171(4):631\u2013639.<\/li>\n<li>Giugliani R <em>et al<\/em>. Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts. <em>Rev Assoc Med Bras<\/em>. 2010;56(3):271\u2013277.<\/li>\n<li>Giugliani R Federhen A, Rojas MV, et al. Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment. <em>Genet Mol Biol<\/em> 2010;33(4):589\u2013604. doi:10.1590\/S1415-47572010005000093.<\/li>\n<li>Giugliani R <em>et al<\/em>. Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America. <em>Genet Mol Biol<\/em> 2014;37(2):315\u2013329.<\/li>\n<li>Guill\u00e9n-Navarro E<em> et al<\/em>. Clinical practice guideline for the management of Hunter syndrome. Hunter Espa\u00f1a working group. <em>Med Clin (Barc)<\/em> 2013;141(10):453.e1\u201313.<\/li>\n<li>Jones SA <em>et al<\/em>. HOS Investigators. Mortality and cause of death in mucopolysaccharidosis type II-a historical review based on data from the Hunter Outcome Survey (HOS). <em>J Inherit Metab Dis<\/em>2009;32(4):534\u2013543.<\/li>\n<li>Lampe C <em>et al<\/em>. Long-term experience with enzyme replacement therapy (ERT) in MPS II patients with a severe phenotype: an international case series. <em>J Inherit Metab Dis<\/em> 2014;37(5):823\u2013829.<\/li>\n<li>Malik V <em>et al<\/em>. Tracheostomy in mucopolysaccharidosis type II (Hunter\u2019s Syndrome). <em>Int J Pediatr Otorhinolaryngol<\/em> 2013;77(7):1204-1208.<\/li>\n<li>Muenzer J <em>et al<\/em>. Multidisciplinary management of Hunter syndrome. <em>Pediatrics<\/em> 2009;124(6):e1228-1239.<\/li>\n<li>Muenzer J <em>et al<\/em>. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. <em>Eur J Pediatr<\/em> 2012;171(1):181-188.<\/li>\n<li>Scarpa M <em>et al<\/em>. Hunter Syndrome Europena Expert Council. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. <em>Orphanet J Rare Dis<\/em>. 2011;6:72.<\/li>\n<li>Wraith JE <em>et al<\/em>. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. <em>Eur J Pediatr<\/em> 2008;167(3):267\u2013277.<\/li>\n<li>Yund B <em>et al<\/em>. Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II. <em>Mol Genet Metab<\/em> 2015;114(2):170\u2013177.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1. Hopwood JJ et al. Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate 2-sulphatase gene. <em>Hum Mutat<\/em> 1993;2(6):435\u2013442.<br \/>\n2. Wraith JE <em>et al<\/em>. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy.<em> Eur J Pediatr<\/em> 2008;167(3):267\u2013277.<br \/>\n3. Scarpa M <em>et al<\/em>. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. <em>Orphanet J Rare Dis<\/em> 2011;6:72.<br \/>\n4. Baehner F <em>et al<\/em>. Cumulative incidence rates of the mucopolysaccharidoses in Germany. <em>J Inherit Metab Dis<\/em> 2005;28(6):1011\u20131017.<br \/>\n5. Guffon N <em>et al<\/em>. Diagnosis, quality of life, and treatment of patients with Hunter syndrome in the French healthcare system: a retrospective observational study. <em>Orphanet J Rare Dis<\/em> 2015; 10:43.<br \/>\n6. Chkioua L <em>et al<\/em>. Molecular analysis of iduronate -2- sulfatase gene in Tunisian patients with mucopolysaccharidosis type II. <em>Diagn Pathol<\/em> 2011;6:42.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"MPS-III\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770f044\" class=\"block-wysiwyg\">\n            <h2>MPS III<\/h2>\n<p>Disease name: <strong>Sanfilippo [A, B, C, D]<\/strong> | Deficient enzymes: <strong>Heparan <em>N<\/em>-sulphatase, <\/strong><strong>\u03b1-<em>N<\/em>-acetylglucosaminidase, Acetyl CoA: \u03b1-glucosaminide <em>N<\/em>-acetyltransferase, <\/strong><strong><em>N<\/em>-acetylglucosamine-6-sulphatase <\/strong>| Gene symbol: <em><strong>SGSH, NAGLU, HGSNAT, GNS<\/strong><\/em><\/p>\n<h3>Patients with Mucopolysaccharidosis Type III (MPS III) are at elevated risk for severe morbidity and early mortality<sup>1<\/sup><\/h3>\n<p>MPS III, also known as Sanfilippo syndrome, is caused by a deficiency of 1 of 4 enzymes\u2014heparan <em>N<\/em>-sulphatase, \u03b1-<em>N<\/em>-acetylglucosaminidase, acetyl CoA:\u03b1-glucosaminide <em>N<\/em>-acetyltransferase, and <em>N<\/em>-acetylglucosamine-6-sulphatase\u2014which correlate with the disease\u2019s 4 subtypes, MPS IIIA, IIIB, IIIC, and IIID, respectively. The resulting intracellular accumulation of the glycosaminoglycan (GAG) heparan sulphate leads to progressive multisystemic disease, of which central nervous system degeneration is a hallmark feature.<sup>1,2<\/sup><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770f0a0\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Observed presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Symptoms appear at varying ages depending on the specific enzyme deficiency and rate of disease progression<sup>1<\/sup>: MPS IIIA and IIIB typically appear between ages 1 and 4, while MPS IIIC and IIID typically appear by 7 years of age<sup>1<\/sup><\/li>\n<li>A clinical pattern that includes progressive cognitive decline including speech delay, behavioral problems including aggressiveness, hyperactivity, sleep disorders, and defiant behavior, accompanied by dysmorphic features, cardiomegaly, epilepsy, and\/or orthopedic malformations should prompt testing for MPS III<sup>1<\/sup><\/li>\n<li>Prevalence:\n<ul>\n<li>MPS IIIA is more prevalent in Northern Europe<sup>1<\/sup><\/li>\n<li>MPS IIIB is more prevalent in Southern Europe<sup>1<\/sup> and was also found to have increased prevalence among a Turkish population in Germany<sup>3<\/sup><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Overall disease burden:\n<ul>\n<li>Patients typically experience severe central nervous system deterioration, with slow loss of skills and development of gait disorder, and eventually reach a vegetative state<sup>1<\/sup><\/li>\n<li>Patients have severe behavioural problems between the ages of 3 and 10 years but are physically quite strong and mobile, often making it difficult for caregivers to manage them<sup>2<\/sup><\/li>\n<li>This progressive, debilitating disease places high psychological and financial burdens on patients and their families<sup>1,4<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>General disease progression:\n<ul>\n<li>Developmental delay typically occurs between the ages of 1 and 4<sup>2<\/sup><\/li>\n<li>Affected patients between the ages of 3 and 10 have severe temper tantrums, hyperactivity, sleep disturbances, aggression, and attention deficit<sup>2<\/sup><\/li>\n<li>During the later stages of disease, patients typically have impaired mobility due to joint disease and experience seizures, which can lead to a vegetative state<sup>1,2<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Patients with the most rapidly progressing form of disease often die in the mid-to-late teenage years because of respiratory infection and neurological disease, while other patients may live until their late 30s<sup>1,2<\/sup><\/li>\n<li>Patients with MPS III have mild musculoskeletal abnormalities and therefore require fewer surgical interventions than patients with other MPS subtypes. Patients may undergo:<sup>1<\/sup>\n<ul class=\"sub_page-child\">\n<li>Myringotomies<\/li>\n<li>Hernia surgery<\/li>\n<li>Carpal tunnel surgery<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>MPS III is a polygenic disease, with each subtype associated with a different gene<sup>1,2<\/sup>:\n<ul>\n<li>MPS IIIA is caused by pathogenic variants in the heparan <em>N<\/em>-sulphatase gene, <em>SGSH<\/em>.<\/li>\n<li>MPS IIIB is caused by pathogenic variants in the \u03b1-<em>N<\/em>-acetylglucosaminidase gene,<em> NAGLU<\/em><\/li>\n<li>MPS IIIC is caused by pathogenic variants in the acetyl CoA: \u03b1-glucosaminide <em>N<\/em>-acetyltransferase gene,<em> HGSNAT<\/em><\/li>\n<li>MPS IIID is caused by pathogenic variants in the <em>N<\/em>-acetylglucosamine-6-sulphatase gene, <em>GNS<\/em><\/li>\n<\/ul>\n<\/li>\n<li>These genetic pathogenic variants lead to enzyme deficiency and accumulation of the GAG heparan sulphate<sup>2<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>There are currently no approved drugs for MPS III; however, clinical trials investigating novel therapeutic approaches are ongoing<\/li>\n<li>Available treatment and management recommendations:\n<ul>\n<li>Delaney KA,<em> et al<\/em>. Methods of neurodevelopmental assessment in children with neurodegenerative disease: Sanfilippo syndrome. <em>JIMD Rep<\/em>. 2014;13:129\u2013137.<\/li>\n<li>de Ruijter J, <em>et al<\/em>. Growth in patients with mucopolysaccharidosis type III (Sanfilippo disease). <em>J Inherit Metab Dis<\/em>. 2014;37(3):447\u2013454.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1. Andrade F <em>et al<\/em>. Sanfilippo syndrome: overall review. <em>Pediatr Int<\/em> 2015;57(3):331\u2013338.<br \/>\n2. Yogalingam G <em>et al<\/em>. Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: diagnostic, clinical, and biological implications. <em>Hum Mutat<\/em> 2001;18(4):264\u2013281.<br \/>\n3. Baehner F <em>et al<\/em>. Cumulative incidence rates of the mucopolysaccharidoses in Germany. <em>J Inherit Metab Dis<\/em> 2005;28(6):1011\u20131017.<br \/>\n4. Grant S <em>et al<\/em>. Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID).<em> J Inherit Metab Dis<\/em> 2013;36(2):281\u2013291.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"MPS-IV\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770f11a\" class=\"block-wysiwyg\">\n            <h2>MPS IV<\/h2>\n<p>Disease name: <strong>Morquio A, Morquio B<\/strong> | Deficient enzymes:\u00a0<strong><em>N<\/em>-acetylgalactosamine 6-sulphatase, <\/strong><strong>\u03b2-galactosidase<\/strong>| Gene symbol: <em><strong>GALNS, GLBI<\/strong><\/em><\/p>\n<h3>Early and accurate diagnosis is critical to enable disease-specific intervention<sup>1<\/sup><\/h3>\n<p>Mucopolysaccharidosis Type IV (MPS IV), or Morquio syndrome, is a progressive, multisystemic lysosomal storage disorder resulting from a deficiency of the enzymes <em>N<\/em>-acetylgalactosamine 6-sulphatase or \u03b2-galactosidase that are responsible for the catabolism of glycosaminoglycans (GAGs),<sup>2<\/sup> which are involved in the building of bones, cartilage, skin, tendons, and many other tissues in the body.<sup>3<\/sup> Two distinct forms are recognised: type A (MPS IVA, Morquio A) and type B (MPS IVB). These types differ in the genetic cause of disease, but signs and symptoms among these forms can be similar and present across the spectrum of disease progression.<sup>4<\/sup><\/p>\n<p>MPS IV is progressive, systemic and lifelong, and it can lead to systemic morbidities and a shortened life span.<sup>1<\/sup><br \/>\nPerceived disease rarity, heterogeneous presentation, and variability in disease progression make diagnosis challenging and early intervention critical.<sup>1<\/sup> Regardless of phenotype, symptoms can progress into end organ damage.<\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770f18d\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Typical presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p>Patients with MPS IV, which is commonly perceived as a musculoskeletal condition,<sup>1<\/sup> can present with or develop unpredictable and clinically heterogeneous symptomatology extending well beyond the obvious manifestations.<sup>6<\/sup> The table below illustrates the potential signs and symptoms of Morquio A, which may be observed either alone or in combination with others, and should raise your suspicion of Morquio A.<\/p>\n<p><strong>Download the <a href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Clinical-manifestations-of-Morquio-A-1.pdf?v=0.8\" target=\"_blank\" rel=\"noopener\">Clinical Manifestations of Morquio A<\/a><\/strong><\/p>\n<p>Progressive, systemic manifestations can lead to potentially severe cardiovascular,<sup>1,7\u20139 <\/sup>pulmonary<sup>1,6,7,10,11 <\/sup>neurological,<sup>6,12 <\/sup>musculoskeletal,<sup>1,6 <\/sup>rheumatological,<sup>5,13 <\/sup>ophthalmological<sup>1,14,15<\/sup>\u00a0ENT<sup>1,16<\/sup>\u00a0hepatic\/abdominal,<sup>13<\/sup>\u00a0and dental<sup>6,17<\/sup>\u00a0consequences. In contrast with other MPS disorders, however, patients with MPS IV do not present with cognitive impairment.<\/p>\n<p>Of note, over 70% of patients manifest with unusual skeletal features within the first 2 to 3 years of life.<sup>6<\/sup>\u00a0Recent research has indicated that approximately 25% of patients with Morquio A syndrome present with a non-classical phenotype.<sup>5<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Risk factors\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p>Risk factors for increased morbidity include:<sup>4,5<\/sup><\/p>\n<ul>\n<li>Skeletal dysplasia<\/li>\n<li>Impaired vision\/hearing<\/li>\n<li>Spinal cord compression<\/li>\n<li>Short stature and neck<\/li>\n<li>Respiratory problems<\/li>\n<li>Cardiac problems<\/li>\n<li>Gastrointestinal issues<\/li>\n<li>Endurance and mobility issues<\/li>\n<li>Surgical frequency<\/li>\n<li>Increased surgeries<\/li>\n<\/ul>\n<p>The majority of patients with Morquio A do not survive past the second decade of life, with frequent causes of death including respiratory failure, complications from surgery, and cardiac failure.<sup>1<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <h3>MPS IV: a spectrum of disease progression and presentation<\/h3>\n<p>Patients can present with classical or non-classical patterns of signs and symptoms. Patients with non-classical phenotype are often reported to have significantly delayed time to diagnosis relative to symptom manifestation.<sup>1<\/sup><\/p>\n<p>Variable disease progression in patients with Morquio A<sup>18<\/sup><\/p>\n<p><img decoding=\"async\" class=\"alignnone wp-image-4812 size-full\" src=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/08\/Variable_disease_progression.png?v=0.8\" alt=\"Variable_disease_progression\" width=\"648\" height=\"219\" srcset=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/08\/Variable_disease_progression.png 648w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/08\/Variable_disease_progression-300x101.png 300w\" sizes=\"(max-width: 648px) 100vw, 648px\" \/><\/p>\n<p>Regardless of phenotype,<sup>1<\/sup>\u00a0symptoms can progress into end-stage organ damage.<br \/>\nUnderappreciation of non-classical presentation in Morquio A can lead to delayed or missed diagnoses, with significant impacts:<\/p>\n<ul>\n<li>Severe multisystemic complications<sup>1,19<\/sup><\/li>\n<li>Irreversible or end-organ damage<sup>19<\/sup><\/li>\n<li>Delay in initiating enzyme replacement therapy (ERT) to address underlying enzyme deficiency<sup>20<\/sup><\/li>\n<li>Lack of access to disease-specific management, with concomitant increase in risk of surgical mortality<sup>21-24<\/sup><\/li>\n<\/ul>\n<p><em>Surgical considerations<\/em><\/p>\n<p>Surgical need and burden is high among patients with Morquio A. According to a natural history study of Morquio A, 70% of the population (mean age 14.5 years) had at least 1 surgical procedure.<sup>7<\/sup><\/p>\n<p><strong>Incidence of common surgical procedures for Morquio A population<sup>7,a<\/sup><\/strong><\/p>\n<p><img decoding=\"async\" class=\"alignnone size-medium wp-image-907\" src=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2022\/12\/common_surgical_procedures_graph.svg\" alt=\"common surgical procedures graph\" width=\"300\" height=\"96\" \/><\/p>\n<p><small>Adapted from Harmatz, <em>Mol Genet Metlab<\/em> 2013<br \/>\n<\/small><small>Data based on medical history reviews of 325 patients with Morquio A and a mean age of 14.5 years.<\/small><\/p>\n<p>A patient\u2019s surgical history and need should alert you to the possibility of MPS IV.<\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic Information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <h4>Genetics and pathophysiology<\/h4>\n<p>MPS IVA (Morquio A) and MPS IVB are caused by pathogenic variants in the <em>GALNS<\/em>\u00a0and\u00a0<em>GLB1<\/em>\u00a0genes, which encode the enzymes\u00a0<em>N<\/em>-acetylgalactosamine 6-sulphatase and \u03b2-galactosidase, respectively.<sup>1,25<\/sup>\u00a0The resulting enzyme deficiencies lead to multiple metabolic pathologies including, most notably, the accumulation of the GAG substrates keratan sulphate and chondroitin-6-sulphate in lysosomes throughout the body.<sup>1,26<\/sup><\/p>\n<p><em><strong>Over 220 pathogenic variants identified to date in the GALNS gene give rise to wide genotypic and phenotypic heterogeneity.<sup>1<\/sup><\/strong><\/em><\/p>\n<p>As lysosomes accumulate, they occupy an increasingly greater area of the cytoplasm, obscuring other organelles and disrupting function.<sup>27<\/sup>\u00a0The defective enzyme activity in MPS IV leads to cell, tissue, and organ system dysfunction that results in the progressive multisystemic morbidities that are the hallmark of this disorder.<sup>1,6<\/sup><\/p>\n<p><sup>\u00a0<\/sup><\/p>\n<p><a href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/genetics_and_pathophysiology_2.svg?v=0.8\"><img decoding=\"async\" class=\"alignnone size-medium wp-image-3807\" src=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/genetics_and_pathophysiology_2.svg\" alt=\"\" width=\"300\" height=\"95\" \/><\/a><\/p>\n<p><sup>\u00a0<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p>Ongoing research is transforming patient management:<\/p>\n<ul>\n<li>There is now greater understanding about the need for multidisciplinary, coordinated care and perioperative care and monitoring<sup>1,6<\/sup><\/li>\n<li>ERT is available for Morquio A, which addresses the underlying metabolic deficit<sup>29<\/sup><\/li>\n<\/ul>\n<p><strong>Enzyme Replacement Therapy (ERT)<\/strong><\/p>\n<p>Published in 2014, the \u201cInternational Guidelines for the Management and Treatment of Morquio A Syndrome\u201d establish the standard of care for Morquio A. Due to the progressive nature of the disease, these guidelines urge early initiation of treatment with ERT.<\/p>\n<p>In addition to ERT, ongoing lifetime management and procedural care from a multidisciplinary coordinated care team are critical components to optimising patient outcomes.<sup>6<\/sup>\u00a0Supportive care includes both medications and surgical interventions, including the following:<sup>1,6,7<\/sup><\/p>\n<ul>\n<li>Nonsteroidal anti-inflammatory drugs for joint pain<\/li>\n<li>Antibiotics for pulmonary infection<\/li>\n<li>Oxygen supplementation for pulmonary compromise and obstructive sleep apnea<\/li>\n<li>Cervical spine fusion and\/or decompression<\/li>\n<li>Femoral osteotomies for straightening of the legs<\/li>\n<li>Corrective knee surgery for severe genu valgum deformity<\/li>\n<\/ul>\n<p>Due to the unpredictable, multisystemic nature of MPS IVA, regular, multidisciplinary, comprehensive evaluation and treatment from a coordinated care team is also essential to identify signs of organ damage and ensure optimal patient outcomes.<sup>1,6<\/sup><\/p>\n<p>Physicians can optimise their management by creating a personalised management plan for each of their patients, starting with a thorough assessment schedule for each body system affected by MPS IVA.<sup>1<\/sup><\/p>\n<p><strong>Download <a href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Ongoing-multisystemic-assessments-in-patients-with-Morquio-A.pdf?v=0.8\" target=\"_blank\" rel=\"noopener\">On-going multisystemic assessments in patients with Morquio A<\/a><\/strong><\/p>\n<p>Once diagnosis is confirmed, baseline assessments should be performed and ERT should be promptly initiated. ERT can significantly improve endurance, as measured by the 6-Minute Walk Test (6MWT). Significant change in the 6MWT reflects improvement or decline in the functional status of the cardiac, respiratory, and musculoskeletal systems and a change in disease progression.<sup>1,26<\/sup>\u00a0Beyond ERT, ongoing comprehensive assessments, symptomatic treatment, and surgical interventions,<sup>1,7<\/sup>\u00a0continuity of care from the paediatric to the adult setting is a critical consideration for patients and families living with MPS.<sup>1,30<\/sup><\/p>\n<h4>Surgical considerations<\/h4>\n<p>Patients with MPS IV often require surgical intervention to address the multisystemic complications of the disease.<sup>7<\/sup>\u00a0This surgical care is complicated by the nature of the disease.<\/p>\n<p>Patients with MPS IV suffer from multiple factors that can dramatically increase surgical risk and the need for monitoring:<sup>31<\/sup><\/p>\n<ul>\n<li>Reduced respiratory capacity<\/li>\n<li>Impaired cardiovascular function<\/li>\n<li>Skeletal morphology<\/li>\n<li>Cervical spinal instability<\/li>\n<li>Complex airway structure<\/li>\n<\/ul>\n<p>These factors complicate surgical and anesthetic care, require preplanning, and necessitate disease-specific techniques to increase optimal outcomes.<sup>31<\/sup><\/p>\n<p><em><strong>The benefits of a procedure in patients with MPS IV should always be balanced against the associated risks.<sup>31<\/sup><\/strong><\/em><\/p>\n<p>Specialized perioperative procedures during anesthesia, such as intubation and extubation, and the use of an intraoperative neuromonitoring checklist, are essential to successful surgical interventions.<sup>1,31<\/sup>\u00a0An integrated surgical team consisting of MPS VI specialists is crucial for positive, durable outcomes.<sup>1<\/sup><\/p>\n<h4>Transitioning to adult care<\/h4>\n<p>As patients with MPS IV reach adulthood, their relationship with their medical team will change. To help manage this transition, individual plans are necessary to minimise treatment interruptions, extend support beyond the scope of paediatric care and parental support, and ensure that adult patients are knowledgeable in managing MPS IV.<sup>1,30<\/sup><\/p>\n<p>These transition plans should be tailored to each patients specific needs, so that those who can take over their own care will have the necessary tools, and those who are more limited will have the appropriate care and services in place to support them. The plans should include an assessment to determine the patients capacity to successfully achieve his or her outlined goals, as well as his or her knowledge and ability to communicate information about their\u00a0condition.<sup>30<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1. Hendriksz CJ <em>et al<\/em>. International guidelines for the management and treatment of Morquio A syndrome. <em>Am J Med Genet Part A<\/em> 2014;9999A:1\u201315.<br \/>\n2. Northover H <em>et al<\/em>. Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. <em>J Inherit Metab Dis<\/em> 1996;19(3):357\u2013365.<br \/>\n3. Islam T <em>et al<\/em>. Chemistry, biochemistry, and pharmaceutical potentials of glycosaminoglycans and related saccharides. In: Wong C-H, ed. Carbohydrate-based Drug Discovery Weinheim, Germany: WILEY-VCH Verlag GmbH &amp; Co KGaA; 2003:407\u2013439.<br \/>\n4. Tomatsu S <em>et al<\/em>. Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A). <em>Hum Mutat<\/em> 2005;26(6):500\u2013512.<br \/>\n5. Monta\u00f1o AM <em>et al<\/em>. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease.<em> J Inherit Metab Dis<\/em> 2007;30(2):165-174.<br \/>\n6. Tomatsu S <em>et al<\/em>. Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment: a special review. <em>Curr Pharm Biotechnol<\/em> 2011;12(6):931\u2013945.<br \/>\n7. Harmatz P <em>et al<\/em>. The Morquio A clinical assessment program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. <em>Mol Genet Metab<\/em> 2013;109(1):54\u201361.<br \/>\n8. John RM <em>et al.<\/em> Echocardiographic abnormalities in type IV mucopolysaccharidosis. <em>Arch Dis Child<\/em> 1990;65(7):746\u2013749.\u00a0 9. Ireland MA, Rowlands DB. Mucopolysaccharidosis type IV as a cause of mitral stenosis in an adult. <em>Br Heart J<\/em> 1981;46(1):113\u2013115.<br \/>\n10. Semenza GL, Pyeritz RE. Respiratory complications of mucopolysaccharide storage disorders. <em>Medicine<\/em> 1988;67(4):209\u2013219.<br \/>\n11. Pelley CJ <em>et al<\/em>. Tracheomalacia in an adult with respiratory failure and Morquio syndrome. <em>Respir Care<\/em> 2007;52(3):278\u2013282.<br \/>\n12. Gulati MS et al. Morquio syndrome: a rehabilitation perspective. <em>J Spinal Cord Med<\/em> 1996;19(1):12\u201316.<br \/>\n13. Holzgreve W et al. Morquio syndrome: clinical findings in 11 patients with MPS IVA and 2 patients MPS IVB. <em>Hum Genet<\/em> 1981;57(4):360\u2013365.<br \/>\n14. Danes BS. Corneal clouding in the genetic mucopolysaccharidoses: a cell culture study. <em>Clin Genet<\/em> 1973;4(1):1\u20137.<br \/>\n15. Leslie T <em>et al<\/em>. Morquio syndrome: electron microscopic findings [letter]. <em>Br J Ophthalmol<\/em> 2005;89(7):917\u2013929.<br \/>\n16. Hendriksz CJ <em>et al<\/em>. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. <em>Mol Genet Metab<\/em> 2013;110:54\u201364.<br \/>\n17. Kinirons MJ, Nelson J. Dental findings in mucopolysaccharidosis type IV A (Morquio&#8217;s disease type A). <em>Oral Surg Oral Med Oral Pathol<\/em> 1990;70(2):176\u2013179.<br \/>\n18. Data on file. BioMarin Pharmaceutical Inc.<br \/>\n19. Berger KI <em>et al<\/em>. Respiratory and sleep disorders in mucopolysaccharidosis. <em>J Inherit Metab Dis<\/em> 2013;36(2):201\u2013210.<br \/>\n20. Hendriksz C. Improved diagnostic procedures in attenuated mucopolysaccharidosis. <em>Br J Hosp Med<\/em> 2011;72(2):91\u201395.<br \/>\n21. Clarke LA. Pathogenesis of skeletal and connective tissue involvement in the mucopolysaccharidoses: glycosaminoglycan storage is merely the instigator. <em>Rheumatology<\/em> (Oxford) 2011;50(suppl 5):v13\u201318.<br \/>\n22. Lehman TJA <em>et al<\/em>. Diagnosis of the mucopolysaccharidoses. <em>Rheumatology<\/em> 2011;50(suppl 5):v41\u2013v48.<br \/>\n23. Morishita K, Petty RE. Musculoskeletal manifestations of mucopolysaccharidoses. <em>Rheumatology<\/em> 2011;50(suppl 5):v19\u2013v25.<br \/>\n24. Muenzer J. Overview of the mucopolysaccharidoses. <em>Rheumatology<\/em> (Oxford). 2011;50(suppl 5):v4\u2013v12.<br \/>\n25. Wood TC <em>et al<\/em>. Diagnosing mucopolysaccharidosis IVA. J <em>Inherit Metab Dis<\/em> 2013;36(2):293\u2013307.<br \/>\n26. VIMIZIM [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2014.<br \/>\n27. Coutinho MF <em>et al.<\/em> Glycosaminoglycan storage disorders: a review. <em>Biochem Res Int<\/em> 2012;2012:471325.<br \/>\n28. Bank RA <em>et al<\/em>. Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen perturbations in cartilage of Morquio syndrome A patients. <em>Mol Genet Metab<\/em> 2009;97(3):196\u2013201.<br \/>\n29. Harmatz P <em>et al<\/em>. Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome. <em>Mol Genet Metab<\/em> 2015;114(2):186\u2013194.<br \/>\n30. American Academy of Pediatrics, American Academy of Family Physicians, American College of Physicians, Transitions Clinical Report Authoring Group, Cooley WC, Sagerman PJ. Supporting the health care transition from adolescence to adulthood in the medical home. <em>Pediatrics<\/em> 2011;128(1):182\u2013200.<br \/>\n31. Theroux MC <em>et al<\/em>. Anesthetic care and perioperative complications of children with Morquio syndrome. <em>Paediatr Anaesth<\/em> 2012;22(9):901\u2013907.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"MPS-VI\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770f1dc\" class=\"block-wysiwyg\">\n            <h2>MPS VI<\/h2>\n<p>Disease name: <strong>Maroteaux-Lamy<\/strong> | Deficient enzymes:\u00a0<strong><em>N<\/em>-acetylgalactosamine 4-sulphatase<\/strong> | Gene symbol: <em><strong>ARSB<\/strong><\/em><\/p>\n<h3>Cause and effects of MPS VI: an overview<\/h3>\n<h4>Early and accurate diagnosis is critical to enable disease-specific intervention<\/h4>\n<p>Mucopolysaccharidosis Type VI (MPS VI), or Maroteaux-Lamy syndrome, is a devastating, progressive and heterogeneous disorder with severe pathologies affecting multiple organs. It is caused by deficient activity of N-acetylgalactosamine-4-sulphatase (also known as arylsulphatase B [ASB]), the enzyme that catabolises the glycosaminoglycans (GAGs) dermatan sulphate and chondroitin sulphate.<sup>1,2<\/sup><\/p>\n<p>Although there is wide variability in the phenotypic presentation of MPS VI,<sup>1,2<\/sup>\u00a0patients are often characterised as having either rapidly or slowly progressing disease:<\/p>\n<ul>\n<li>Rapidly progressing MPS VI is characterised by an early onset, typically before 2 or 3 years of age. If untreated, most individuals do not live to adulthood (second and third decade)<sup>1,2<\/sup><\/li>\n<li>Individuals with slowly progressing disease typically develop symptoms in the teenage years or early adulthood<sup>2<\/sup><\/li>\n<\/ul>\n<p>Regardless of rate of progression, untreated MPS VI can progress over years and lead to:<sup>3<\/sup><\/p>\n<ul>\n<li>Skeletal deformities<\/li>\n<li>Joint disease<\/li>\n<li>Cardiopulmonary disease<\/li>\n<li>Blindness<\/li>\n<li>Spinal cord compression<\/li>\n<li>Inability to walk<sup>4<\/sup><\/li>\n<\/ul>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"MPS-VI\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Observed presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <h4>Typical presentation<\/h4>\n<p>MPS VI is a clinically heterogeneous condition in which patients can present with marked disease in the first year of life or with disease that progresses more slowly, with symptoms presenting over a longer period of time. However, it is important to recognise that MPS VI manifests symptoms along a continuum, so there are no fixed parameters for these categories of disease progression.<sup>1,2<\/sup><\/p>\n<p>Rapidly progressing MPS VI, characterised in the cross-sectional survey study by Swiedler\u00a0<em>et al<\/em>\u00a0as urinary levels of GAG protein (uGAG) above 200 \u03bcg\/mg,<sup>3<\/sup>\u00a0can manifest in the first year of life with nonspecific symptoms. Between years 2 and 3, characteristic features develop, including:<sup>1,2,5<\/sup><\/p>\n<ul>\n<li>Coarse facial appearance with diffuse and coarse hair<\/li>\n<li>Flat bridge of the nose<\/li>\n<li>Wide, anteverted nostrils<\/li>\n<li>Thick lips<\/li>\n<li>Macroglossia<\/li>\n<\/ul>\n<p>Slowly progressing MPS VI, characterised as uGAG levels less than or equal to 200 \u03bcg\/mg, may not overtly present, thus delaying diagnosis until later in life. Nevertheless, patients develop significant morbidity that may be life limiting and life threatening. Whether rapidly or slowly progressing, MPS VI does not typically cause neurocognitive deficits, although physical limitations can affect patients\u2019 learning and development.<sup>3<\/sup><\/p>\n<p>The table below outlines complications of MPS VI by organ system. The clinical manifestations associated with MPS VI are heterogeneous; however, all patients will experience disease progression.<\/p>\n<p><strong>Download <a href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Clinical-manifestations-of-MPS-VI.pdf?v=0.8\" target=\"_blank\" rel=\"noopener\">Clinical Manifestations of MPS VI<\/a><\/strong><\/p>\n<p>Patients with MPS VI express markedly lower growth rates than unaffected age-adjusted peers. The deviation in growth experienced by patients with MPS VI may be a sign of secondary problems and should prompt clinical surveillance for issues such as malnutrition, endocrine abnormalities or psychosocial deprivation.<\/p>\n<p><img decoding=\"async\" class=\"alignnone size-medium wp-image-3796\" src=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Growth-comparison-between-patients-with-rapidly-progressing-MPS-VI-and-unaffected-age-adjusted-peers-300x188.png\" alt=\"Growth comparison between patients with rapidly progressing MPS-VI\" width=\"300\" height=\"188\" srcset=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Growth-comparison-between-patients-with-rapidly-progressing-MPS-VI-and-unaffected-age-adjusted-peers-300x188.png 300w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Growth-comparison-between-patients-with-rapidly-progressing-MPS-VI-and-unaffected-age-adjusted-peers-1024x640.png 1024w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Growth-comparison-between-patients-with-rapidly-progressing-MPS-VI-and-unaffected-age-adjusted-peers-768x480.png 768w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Growth-comparison-between-patients-with-rapidly-progressing-MPS-VI-and-unaffected-age-adjusted-peers.png 1500w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <h4>Progression of MPS VI<sup>12<\/sup><\/h4>\n<p>MPS VI is a clinically heterogeneous condition with a spectrum of phenotypes that have variable onset and rates of progression.<sup>2<\/sup>\u00a0The figure below demonstrates the wide variability between a rapidly progressing patient and a slowly progressing patient. The rapidly progressing patient displays many of the phenotypic hallmarks of MPS VI.<\/p>\n<p><img decoding=\"async\" class=\"alignnone wp-image-2224 size-large\" src=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/01\/Rate-of-Progression--1024x675.jpg\" alt=\"Images showing photos of the rate of progression\" width=\"1024\" height=\"675\" srcset=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/01\/Rate-of-Progression--1024x675.jpg 1024w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/01\/Rate-of-Progression--300x198.jpg 300w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/01\/Rate-of-Progression--768x506.jpg 768w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/01\/Rate-of-Progression--1500x989.jpg 1500w, https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/01\/Rate-of-Progression-.jpg 1517w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/p>\n<p>Differentiation into rapidly and slowly progressing disease is only apparent in extreme cases. If left untreated, disease progression will inhibit physical and functional well-being and results in a markedly shortened life span.<sup>4<\/sup><\/p>\n<p>Regardless of phenotype, affected individuals progress over the course of years and ultimately experience:<sup>4<\/sup><\/p>\n<ul>\n<li>Serious loss of mobility requiring use of a wheelchair or bed rest<\/li>\n<li>Cardiopulmonary disease<\/li>\n<li>Blindness<\/li>\n<li>Spinal cord compression<\/li>\n<li>Early mortality<\/li>\n<\/ul>\n<p>Patients with MPS VI usually die from infections, complications secondary to surgery or cardiopulmonary disease.<sup>4<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <h4>Genetics and pathophysiology<\/h4>\n<p>MPS VI is an autosomal recessive condition caused by a deficiency of the enzyme\u00a0<em>N<\/em>-acetylgalactosamine 4-sulphatase (also known as ASB). This deficiency results in the accumulation of the GAG dermatan sulphate in the lysosomes of a wide range of tissues.<sup>13,14<\/sup><\/p>\n<p><em><strong>Clinical manifestations of MPS VI are related to progressive accumulation of dermatan sulphate and sulphated oligosaccharides derived from both dermatan sulphate and chondroitin sulphate in lysosomes, cells and tissues.<sup>2<\/sup><\/strong><\/em><\/p>\n<p>No specific ethnic group has been associated with an increased risk of MPS VI; however, some increased frequencies of specific pathogenic variants have been reported. There is a common pathogenic variants (1533del23) found in 23% of alleles in Brazilian patients with MPS VI. Additionally, one study demonstrated a high birth prevalence of MPS VI in the Turkish population living in Germany, as compared with the non-Turkish German population.<sup>2<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <h4>Management considerations for patients with MPS VI<\/h4>\n<p>Over the past decade, the management of MPS VI has evolved along with clinicians\u2019 knowledge about the disease, such as its phenotypic variability and progression. Other factors, such as patients living into adulthood, highlight new areas for research, understanding and promise in management.<\/p>\n<p>MPS VI affects multiple body systems, making management of a diverse spectrum of disease manifestations an important part of providing integrated care. Management should include use of adaptive or supportive devices, physical and occupational therapy, symptom-based medications, surgical interventions and treatment to provide the deficient enzyme.<sup>4<\/sup><\/p>\n<h4><em>Management guidelines<\/em><\/h4>\n<p>Published in 2007, the \u201cManagement Guidelines for Mucopolysaccharidosis\u201d provides recommendations across specialties for the management of patients with MPS VI. It recommends enzyme replacement therapy (ERT) as a treatment option to be considered in patients with MPS VI.<sup>4<\/sup><\/p>\n<p>In addition to initiating ERT where appropriate, the guidelines recommend system-specific management strategies for symptoms associated with GAG buildup.<sup>4<\/sup><\/p>\n<p>Lifetime management and procedural care from a multidisciplinary coordinated care team are critical components to optimising patient outcomes.<sup>14,15<\/sup>\u00a0Patients with MPS VI require early and regular assessments to evaluate disease progression across multiple organ systems and to detect and treat potential complications of the disease.<sup>4<\/sup><\/p>\n<p><strong>Download <a href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/wp-content\/uploads\/sites\/2\/2023\/05\/Recommended-schedule-of-assesments-for-patients-with-MPS-VI.pdf?v=0.8\" target=\"_blank\" rel=\"noopener\">the schedule of assessments for patients with MPS VI recommended by the 2007 guidelines.<\/a><\/strong><\/p>\n<h4><em>Surgical considerations<\/em><\/h4>\n<p>Patients with MPS VI often require surgical intervention to address the multisystemic complications of the disease. This surgical care is complicated by the nature of the disease.<sup>15<\/sup><\/p>\n<p class=\"margin_spl\">Patients with MPS VI suffer from multiple factors that can dramatically increase surgical risk and the need for monitoring, including:<sup>15<\/sup><\/p>\n<ul>\n<li>Reduced respiratory capacity<\/li>\n<li>Impaired cardiovascular function<\/li>\n<li>Skeletal morphology<sup>4<\/sup><\/li>\n<li>Complex airway structure<\/li>\n<\/ul>\n<p>These factors complicate surgical and anaesthetic care, require preplanning and necessitate disease-specific techniques to increase optimal outcomes.<sup>16<\/sup><\/p>\n<p><em><strong>The benefits of a procedure in patients with MPS VI should always be balanced against the associated risks.<sup>15<\/sup><\/strong><\/em><\/p>\n<p>Specialised perioperative procedures during anaesthesia, such as intubation and extubation, and use of an intraoperative neuromonitoring checklist are essential to successful surgical interventions. An integrated surgical team consisting of MPS VI specialists is critical for positive, durable outcomes.<sup>15,16<\/sup><\/p>\n<h4><em>Transitioning to adult care<\/em><\/h4>\n<p>As patients with MPS VI reach adulthood, their relationship with their medical team will change. To help manage this transition, individual plans are necessary to minimise treatment interruptions, extend support beyond the scope of paediatric care and parental support, and ensure that adult patients are knowledgeable in managing MPS VI.<sup>17<\/sup><\/p>\n<p>These transition plans should be tailored to each patient\u2019s specific needs, so that those who can take over their own care will have the necessary tools and those who are more limited will have the appropriate care and services in place to support them. The plans should include an assessment to determine the patient\u2019s capacity to achieve their\u00a0outlined goals, as well as their\u00a0knowledge and ability to communicate information about their\u00a0condition.<sup>17<\/sup><\/p>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1.\u00a0Th\u00fcmler A\u00a0<i>et al<\/i>. Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series.\u00a0<em>J Inherit Metab Dis<\/em>\u00a02012;35(6):1071-1079.<br \/>\n2.\u00a0Valayannopoulos V\u00a0<i>et al<\/i>. Mucopolysaccharidosis VI.\u00a0<em>Orphanet J Rare Dis<\/em> 2010;5:5.<br \/>\n3.\u00a0Swiedler SJ\u00a0<i>et al<\/i>. Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with mucopolysaccharidosis VI (Maroteaux\u2013Lamy syndrome).\u00a0<em>Am J Med Genet A<\/em>\u00a02005;134A(2):144-150.<br \/>\n4.\u00a0Giugliani R\u00a0<i>et al<\/i>. Management guidelines for mucopolysaccharidosis VI.\u00a0<em>Pediatrics<\/em> 2007;120:405-418. \u00a05.\u00a0Muhlebach MS\u00a0<i>et al<\/i>. Respiratory manifestations in mucopolysaccharidoses.\u00a0<em>Paediatr Respir Rev<\/em>\u00a02011;12(2):133-138.<br \/>\n6.\u00a0Lin H-Y\u00a0<i>et al<\/i>. Polysomnographic characteristics in patients with mucopolysaccharidoses.\u00a0<em>Pediatr Pulmonol<\/em>. 2010;45(12):1205-1212.<br \/>\n7.\u00a0Kampmann C<i>et al<\/i>. Mucopolysaccharidosis VI: cardiac involvement and the impact of enzyme replacement therapy.\u00a0<em>J Inherit Metab Dis<\/em>\u00a02014;37(2):269-276.<br \/>\n8.\u00a0Willoughby CE\u00a0<i>et al<\/i>. Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function \u2014 a review.\u00a0<em>Clin Exper Ophthalmol<\/em>. 2010;38(suppl 1):2-11.<br \/>\n9.\u00a0Ganesh A\u00a0<i>et al<\/i>. An update on ocular involvement in mucopolysaccharidoses.\u00a0<em>Curr Opin Ophthalmol<\/em>\u00a02013;24(5):379-388.<br \/>\n10.\u00a0Kantaputra PN\u00a0<i>et al<\/i>. Oral manifestations of 17 patients affected with mucopolysaccharidosis type VI.\u00a0<em>J Inherit Metab Dis<\/em>\u00a02014;37(2):263-268.<br \/>\n11.National Institute of Neurological Disorders and Stroke Mucopolysaccharidoses Fact Sheet. http:\/\/www.ninds.nih.gov\/disorders\/mucopolysaccharidoses\/detail_mucopolysaccharidoses.htm. Accessed November 2016.<br \/>\n12.\u00a0Data on file. BioMarin Pharmaceutical Inc.<br \/>\n13.\u00a0NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2013.<br \/>\n14.\u00a0Giugliani R\u00a0<i>et al<\/i>. Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) \u2014 10-year follow-up of patients who previously participated in an MPS VI Survey Study.\u00a0<em>Am J Med Genet A<\/em>\u00a02014;164A(8):1953-1964.<br \/>\n15.\u00a0Walker R\u00a0<i>et al<\/i>. Anaesthesia and airway management in mucopolysaccharidosis.\u00a0<em>J Inherit Metab Dis<\/em>\u00a02013;36(2):211-219.<br \/>\n16.\u00a0Vitale MG\u00a0<i>et al<\/i>. Delphi Consensus Report: Best practices in intraoperative neuromonitoring in spine deformity surgery: development of an intraoperative checklist to optimize response.\u00a0<em>Spine Deformity<\/em>. 2014;2(5):333-339. \u00a017.\u00a0American Academy of Pediatrics, American Academy of Family Physicians, American College of Physicians, Transitions Clinical Report Authoring Group, Cooley WC, Sagerman PJ. Supporting the health care transition from adolescence to adulthood in the medical home.\u00a0<em>Pediatrics<\/em> 2011;128(1):182-200.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"MPS-VII\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770f646\" class=\"block-wysiwyg\">\n            <h2>MPS VII<\/h2>\n<p>Disease name: <strong>Sly<\/strong> | Deficient enzymes: <strong>\u03b2-glucuronidase<\/strong> | Gene symbol: <em><strong>GUSB<\/strong><\/em><\/p>\n<h3>Patients with Mucopolysaccharidosis Type VII (MPS VII) are at elevated risk for severe morbidity and early mortality<sup>1<\/sup><\/h3>\n<p>MPS VII, also known as Sly syndrome, is a progressive, multisystemic disease caused by a deficiency of the enzyme \u03b2-glucuronidase, which is required for the degradation of the glycosaminoglycans (GAGs) heparan sulphate, dermatan sulphate, and chondroitin sulphate.<sup>1<\/sup><br \/>\nMPS VII can present as early as birth with hydropsis fetalis, or as a young child or adolescent with delayed motor development, mild to severe cognitive impairment and multiorgan disease.<sup>1-4<\/sup><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770f6ac\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Observed presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Symptoms appear at varying ages, depending on rate of disease progression:\n<ul>\n<li>Rapidly progressing, birth<sup>1<\/sup><\/li>\n<li>Slowly progressing, late infancy to adolescence<sup>1-3<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Observed presentation includes:<sup>1,2,4,5<\/sup>\n<ul>\n<li>Coarse facial features<\/li>\n<li>Hepatosplenomegaly<\/li>\n<li>Gibbus deformity<\/li>\n<li>Diastasis recti<\/li>\n<li>Hernia<\/li>\n<li>Short stature<\/li>\n<li>Cognitive impairment<\/li>\n<li>Frequent respiratory infections<\/li>\n<li>Mild to moderate dysostosis multiplex<\/li>\n<li>Corneal clouding<\/li>\n<li>Hearing loss<\/li>\n<li>Speech loss<\/li>\n<li>Cardiac valve abnormalities<\/li>\n<\/ul>\n<\/li>\n<li>Specific recommendations for consideration of MPS VII include:\n<ul>\n<li>Infants presenting with hydrops fetalis at birth should be considered<sup>1,4<\/sup><\/li>\n<li>In reported cases, coarse facial features, developmental delay, hepatosplenomegaly, and cardiac valve abnormalities prompted testing<sup>2,5,6<\/sup><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Overall disease burden:\n<ul>\n<li>Patients experience multiorgan dysfunction and possibly cognitive decline, with a resulting high disease burden<sup>2\u20135<\/sup><\/li>\n<li>Patients can lose their ability to independently ambulate, communicate, and care for themselves, thereby increasing caregiver needs<sup>4,6,7<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Rapidly progressing patients:\n<ul>\n<li>Disease presents at birth with hydrops fetalis and severe cognitive impairment<sup>1<\/sup><\/li>\n<li>Patients have been reported to die early in life, within a year of birth, due to hydrops fetalis<sup>1<\/sup><\/li>\n<\/ul>\n<\/li>\n<li>Slowly progressing patients:\n<ul>\n<li>Disease presents with coarse facial features, developmental delay, hepatosplenomegaly, and cardiac valve abnormalities<sup>2,4<\/sup><\/li>\n<li>As the disease progresses, patients can also experience cognitive decline, loss of ambulation, loss of ability to take care of themselves, and loss of ability to communicate<sup>4,6,7<\/sup><\/li>\n<li>Patients can survive into their 50s; death has been reported to be associated with cardiac or pulmonary failure<sup>1,4,7 <\/sup><\/li>\n<\/ul>\n<\/li>\n<li>There is no conclusive information on the most frequent types of surgeries patients with MPS VII undergo, but the following have been detailed in case reports:<sup>4,5,7<\/sup>\n<ul>\n<li>Tracheostomy<\/li>\n<li>Scoliosis repair surgery<\/li>\n<li>Cervical fusion<\/li>\n<\/ul>\n<\/li>\n<li>Because patients with MPS often experience anaesthetic complications due to obstructed airways, care must be taken for patients undergoing surgery<sup>8<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>MPS VII is caused by pathogenic variants in the \u03b2-glucuronidase gene, <em>GUSB<\/em><sup>1<\/sup><\/li>\n<li>There are 16 known pathogenic variants within <em>GUSB<\/em><sup>9<\/sup><\/li>\n<li>Pathogenic variants in <em>GUSB<\/em> and resulting enzyme deficiency leads to accumulation of the GAGs heparan sulphate, dermatan sulphate, and chondroitin sulphate<sup>1<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>There are currently no approved therapies for MPS VII; new approaches for the treatment of MPS VII are under clinical investigation<\/li>\n<li>Available treatment and management recommendations:\n<ul class=\"sub_page-child\">\n<li>Bernsen PLJA, <em>et al<\/em>. Phenotypic expression in mucopolysaccharidosis VII. <em>J Neurol Neurosurg Psychiatry<\/em> 1987;50(6):699\u2013703.<\/li>\n<li>Gniadek TJ,<em> et al<\/em>. Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome). <em>Cardiovasc Pathol<\/em> 2015;24(5):322\u2013326. doi:10.1016\/j.carpath.2015.06.001.<\/li>\n<li>Tomatsu S, <em>et al<\/em>. Mutations and polymorphisms in <em>GUSB<\/em> gene in mucopolysaccharidosis VII (Sly Syndrome) <em> Hum Mutat<\/em>. 2009;30(4):511\u2013519.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1.\u00a0Tomatsu S\u00a0<i>et al<\/i>. Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome).\u00a0<em>Hum Mutat<\/em>\u00a02009;30(4):511-519.<br \/>\n2.\u00a0Gehler J\u00a0<i>et al<\/i>. Mucopolysaccharidosis VII: \u03b2-glucuronidase deficiency.\u00a0<em>Humangenetik<\/em>\u00a01974;23(2):149-158.<br \/>\n3.\u00a0Bernsen PLJA\u00a0<i>et al<\/i>. Phenotypic expression in mucopolysaccharidosis VII.\u00a0<em>J Neurol Neurosurg Psychiatry<\/em>\u00a01987;50(6):699-703.<br \/>\n4.\u00a0Gniadek TJ\u00a0<i>et al<\/i>. Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome).\u00a0<em>Cardiovasc Pathol<\/em>\u00a02015;24(5):322-326.<br \/>\n5.\u00a0Nampoothiri S\u00a0<i>et al<\/i>. Sly disease: mucopolysaccharidosis type VII.\u00a0<em>Indian Pediatr<\/em>\u00a02008;45(10):859-861.<br \/>\n6.\u00a0Yamada Y\u00a0<i>et al<\/i>. Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous A619V mutation.\u00a0<em>Bone Marrow Transplant<\/em>\u00a01998;21(6):629-634.<br \/>\n7.\u00a0Fox JE\u00a0<i>et al<\/i>. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.\u00a0<em>Mol Genet Metab<\/em>\u00a02015;114(2):203-208. \u00a08.\u00a0Muenzer J, Beck M, Eng CM, et al.<em>Genet Med.<\/em>\u00a02011;13(2):95\u2013101. doi:10.1097\/GIM.0b013e3181fea459.<br \/>\n9.\u00a0Online Mendelian Inheritance in Man, OMIM. Baltimore, MD: Johns Hopkins University Press. http:\/\/www.ncbi.nlm.nih.gov\/omim. Updated December 20, 2015. Accessed December 21, 2015.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"MPS-IX\" class=\"block wrapped-content block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-63fcf7770f70c\" class=\"block-wysiwyg\">\n            <h2>MPS IX<\/h2>\n<p>Disease name: <strong>Natowicz<\/strong> | Deficient enzymes: <strong>Hyaluronidase<\/strong>| Gene symbol: <em><strong>HYAL1<\/strong><\/em><\/p>\n<h3>As the rarest mucopolysaccharidosis (MPS) disorder, MPS IX has limited information and very few management guidelines<sup>1<\/sup><\/h3>\n<p>MPS IX, also known at Natowicz syndrome, is caused by a deficiency of the enzyme hyaluronidase, which is required for the degradation of the glycosaminoglycan (GAG) hyaluronan. This GAG is highly expressed in synovial fluid, cartilage, and skin, leading to progressive joint manifestations.<sup>1,2<\/sup><\/p>\n<p>MPS IX can present at varying ages with chronic joint pain unresponsive to anti-inflammatory medication.<sup>1,2<\/sup><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770f74a\" class=\"block accordion block-tight-top block-tight-bottom\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t                                                                                <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Observed presentation\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Symptoms appear at varying ages<sup>1,2<\/sup><\/li>\n<li>Presentations observed to date include:<sup>1,2<\/sup>\n<ul>\n<li>Selective joint pain<\/li>\n<li>Swelling and reduced range of motion<\/li>\n<li>Hyperextensible joints<\/li>\n<\/ul>\n<\/li>\n<li>Short stature has been reported in one case<\/li>\n<li>Suspicion of MPS IX should be raised in patients with chronic joint pain unresponsive to anti-inflammatory drugs, a family history of similarly affected children and\/or MRI showing proliferative synovitis without erosions<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Disease progression\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>Overall disease burden: patients experience chronic joint pain, effusions, cysts, gait abnormalities, and reduced range of motion<sup>1,2<\/sup><\/li>\n<li>Joint problems may progressively worsen due to the continued accumulation of GAGs in the affected tissues<sup>2<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Genetic information\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>MPS IX is caused by a genetic pathogenic variant in the <em>HYAL1<\/em> gene<sup>1<\/sup><\/li>\n<li>There are 2 known pathogenic variants within <em>HYAL1<\/em><sup>3<\/sup><\/li>\n<li>Pathogenic variants in <em>HYAL1<\/em> and resulting enzyme deficiency leads to accumulation of the GAG hyaluronan<sup>1,2<\/sup><\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>Key management considerations\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <ul>\n<li>There are currently no approved therapies for the treatment of MPS IX.<\/li>\n<li>Available treatment and management recommendations:\n<ul>\n<li>Imundo L, <em>et al<\/em>. A complete deficiency of Hyaluronoglucosaminidase 1 (HYAL1) presenting as familial juvenile idiopathic arthritis. <em>J Inherit Metab Dis. <\/em>2011;34(5):1013-1022.<\/li>\n<li>Natowicz MR, <em>et al<\/em>. Clinical and biochemical manifestations of hyaluronidase deficiency.<em> N Engl J Med.<\/em> 1996;335(14):1029-1033.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n                                                    <\/div>\n                    <\/div>\n                                                                            <div class=\"accordion-item\">\n                        <div class=\"accordion-title\">\n                            <div class=\"accordion-trigger\">\n                                <span><\/span>\n                                <span><\/span>\n                            <\/div>\n                            <h2>References:\n<\/h2>\n                        <\/div>\n                        <div class=\"accordion-content\">\n                                                            <p><small>1.\u00a0Imundo L\u00a0<i>et al.<\/i>\u00a0A complete deficiency of Hyaluronoglucosaminidase 1 (HYAL1) presenting as familial juvenile idiopathic arthritis.\u00a0<em>J Inherit Metab Dis<\/em>\u00a02011;34(5):1013\u20131022.<br \/>\n2.\u00a0Natowicz MR\u00a0<i>et al.<\/i>\u00a0Clinical and biochemical manifestations of hyaluronidase deficiency.\u00a0<em>N Engl J Med<\/em>\u00a01996;335(14):1029\u20131033.<br \/>\n3.\u00a0Triggs-Raine B\u00a0<i>et al.<\/i>\u00a0Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX.\u00a0<em>Proc Natl Acad Sci USA<\/em>\u00a01999;96(11):6296\u20136300.<\/small><\/p>\n                                                    <\/div>\n                    <\/div>\n                            \t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770f7fe\" class=\"block call-to-action\">\n    <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"box\" style=\"\">\n\t\t\t\t<div class=\"overlay\"><\/div>\n\t\t\t\t<div class=\"cta-content\">\n\t\t\t\t    \t\t\t\t\t<div class=\"cta-content-main\">\n                        <div class=\"content-block\">\n\t\t\t\t\t        \t\t\t\t\t        \t\t\t\t\t\t        <h2 class=\"h3\">Register to learn more about the different types of MPS.\n<\/h2>\n\t\t\t\t\t\t    \t\t\t\t\t\t    \t\t\t\t\t    <\/div>\n\t\t\t\t\t                                <div class=\"content-block\">\n                                <p><a class=\"button button-ghost button-arrow\" href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/stay-updated\/\" target=\"_self\">Register Now<\/a><\/p>\n                            <\/div>\n\t\t\t\t\t                        <\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-63fcf7770f7bd\" class=\"block references block-tight-top block-tight-bottom\">\n    <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t    \t\t\t    <h4>References:\n<\/h4>\n\t\t\t\t\t\t                <ol>\n                                                                                                                        <li><span>Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. <em>J Pediatr<\/em> 2004;144(suppl 5):S27\u2013S34.\n<\/span><\/li>\n                                                                                                                                                <li><span>Muenzer J, Beck M, Eng CM, <em>et al.Genet Med<\/em>. 2011;13(2):95\u2013101. doi:10.1097\/GIM.0b013e3181fea459.\n<\/span><\/li>\n                                                                                                                                                <li><span>Lehman TJA <em>et al<\/em>. Diagnosis of the mucopolysaccharidoses. <em>Rheumatology<\/em> 2011;50(suppl 5):v41\u2013v48.\n<\/span><\/li>\n                                                                                                                                                <li><span>Clarke LA <em>et al<\/em>. Biomarkers for the mucopolysaccharidoses: discovery and clinical utility. <em>Mol Genet Metab<\/em> 2012;106(4):396\u2013402.\n<\/span><\/li>\n                                                                                                                                                <li><span>Morishita K, Petty RE. Musculoskeletal manifestations of mucopolysaccharidoses. <em>Rheumatology<\/em> 2011;50(suppl 5):v19\u2013v25.\n<\/span><\/li>\n                                                                                                                                                <li><span>Muenzer J <em>et al.<\/em> International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. <em>Pediatrics<\/em> 2009;123(1):19-29.\n<\/span><\/li>\n                                                            <\/ol>\n\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":3,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"class_list":["post-1356","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Types of MPS - BioMarin MPS DSE HCP EN-GB<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/hcp.biomarin.com\/en-gb\/mps\/types-of-mps\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Types of MPS - 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