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Diagnosing MPS VI

Diagnosis of MPS VI is usually prompted through clinical presentation.1

Elevated urinary glycosaminoglycan levels suggest a mucopolysaccharidosis disorder.1 MPS VI is diagnosed by testing arylsulfatase B (ASB) activity in blood or fibroblasts. MPS VI is confirmed when ASB enzyme activity in the leukocytes or fibroblasts is determined to be low as judged against a reference enzyme and the laboratory’s own reference ranges.2

When to suspect MPS VI

Because patients with MPS VI present with a variety of signs and symptoms, it is essential to maintain a high index of suspicion and pay close attention to the medical history.3 Suspicious signs and symptom clusters may include3:

  • Macrocephaly
  • Short stature
  • Enlarged tonsils and adenoids
  • Impaired vision
  • Difficulty swallowing
  • Umbilical or inguinal hernias
  • Heart murmur
  • Dysmorphic facial features
  • Enlarged tongue4
  • Corneal clouding
  • Short neck
  • Noisy breathing
  • Sinopulmonary infections
  • Valve disease

Refer Promptly

Once a clinical suspicion has been raised, all patients with suspected MPS VI should be referred promptly to a geneticist for definitive diagnosis and appropriate counseling.5

Benefits of early diagnosis

When MPS VI is recognized promptly and patients are carefully managed, its harmful effects may be minimized. That’s because early diagnosis of MPS VI can allow for early treatment that optimizes the potential benefits of enzyme replacement therapy with NAGLAZYME® (galsulfase).1 In clinical trials, NAGLAZYME has been shown to improve walking and stair‐climbing.7 This improvement can be maintained with long‐term therapy. A study that measured the 6‐minute walk test in patients with MPS VI, many of whom had been on NAGLAZYME therapy for a long time (an average of 6.8 years), showed that improvements in endurance lasted when patients kept taking NAGLAZYME.8

Learn more about the long-term efficacy of NAGLAZYME »

The dangers of delayed diagnosis

Both the slowly and rapidly progressing forms of MPS VI result in significant declines in physical functioning and well-being, as well as a shortened lifespan.1 A 2018 literature review found the median delay in diagnosis for patients with MPS VI was 4.7 years.9

Once multisystemic damage occurs, it cannot be reversed1. Treatment, however, may help to restore endurance and slow the rate of disease progression.6,7

Growth and skeletal abnormalities are common in undiagnosed MPS VI

  • Accelerated growth in infancy coupled with advanced bone maturation is often followed by slowing growth in the first few years of life and short stature10
  • Final height may range from extreme to mild short stature10
  • MPS disorders have a common radiological expression known as dysostosis multiplex that involves almost all of the bony skeleton11

Cardiac abnormalities: also common in MPS VI1

Cardiac disorders are common in MPS VI and a frequent cause of morbidity and mortality.

  • Cardiac disorders most commonly manifest as progressive valve degeneration with stenosis or insufficiency
  • Other manifestations include:
    • Electrocardiographic abnormalities
    • Systemic vascular narrowing and hypertension
    • Endocarditis

Learn more about caring for patients with MPS VI »

References:

  1. Akyol MU, Alden TD, Amartino H, et al. Recommendations for the management of MPS VI: systematic evidence- and consensus-based guidance. Orphanet J Rare Dis. 2019;14:118.
  2. Wood T, Bodamer OA, Curin MG, D’Almeida V, et al. Expert recommendations for the laboratory diagnosis of MPS VI. Mol Genet Metab. 2012;106(1):73-82.
  3. Wilcox WR. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr. 2004;144(5 suppl):S3-S14.
  4. Alpoz AR, Çoker M, Çelen E, et al. The oral manifestations of Maroteaux-Lamy syndrome (mucopolysaccharidosis VI): a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(5):632-637
  5. Harmatz PR. Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). Medscape website. https://emedicine.medscape.com/article/946474-overview. Updated March 20, 2017. Accessed May 2023.
  6. Harmatz P, Giugliani R, Schwartz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr. 2006;148(4):533-539.
  7. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2019.
  8. Giugliani R, Lampe C, Guffon N, et al. Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome)–10-year follow-up of patients who previously participated in an MPS VI Survey Study. Am J Med Genet A. 2014;164A(8):1953-1964. doi: 10.1002/ajmg.a.36584.
  9. Clarke L, Ellaway C, Foster HE, et al. Understanding the early presentation of mucopolysaccharidoses disorders: results of a systematic literature review and physician survey. J Inborn Errors Metab Screen. 2018;6:1-12 (supplemental file).
  10. Heron D, Baumann C, Benichou JJ, Harpey JP, Le Merrer M. Early diagnosis of Maroteaux-Lamy syndrome in two patients with accelerated growth and advanced bone maturation. Eur J Pediatr. 2004;163(6):323-326.
  11. White KK. Orthopaedic aspects of mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v26-v33.

IMPORTANT SAFETY INFORMATION

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. These reactions have occurred during and up to 24 hours after completion of the NAGLAZYME infusion. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Administration of NAGLAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions, including anaphylaxis.

Initiate NAGLAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue NAGLAZYME and immediately initiate appropriate medical treatment, including use of epinephrine. In patients who have experienced anaphylaxis or other severe allergic reactions during infusion with NAGLAZYME, caution should be exercised upon rechallenge. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.

Immune-Mediated Reactions
As with other enzyme replacement therapies, immune-mediated reactions, including membranous glomerulonephritis have been observed. In clinical trials, nearly all patients developed antibodies as a result of treatment with NAGLAZYME; however, no consistent predictive relationship between total antibody titer, neutralizing or IgE antibodies, and infusion-associated reactions, urinary glycosaminoglycan (GAG) levels, or endurance measures has been found.

Risk of Acute Cardiorespiratory Failure
Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload because congestive heart failure may result. Consider a decreased total infusion volume and infusion rate when administering NAGLAZYME to these patients.

Acute Respiratory Complications Associated with Administration
Consideration to delay NAGLAZYME infusion should be given when treating patients who present with an acute febrile or respiratory illness. Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes. Evaluation of airway patency should be considered prior to the initiation of treatment. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction, or extreme drowsiness/sleep induced by antihistamine use.

Infusion Reactions
Pretreatment with antihistamines with or without antipyretics is recommended prior to the start of infusion to reduce the risk of infusion reactions. If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antihistamines and/or antipyretics is recommended.

Spinal or Cervical Cord Compression
Spinal/cervical cord compression is a known and serious complication that is expected to occur during the natural course of MPS VI. Signs and symptoms of spinal/cervical cord compression include back pain, paralysis of limbs below the level of compression, and urinary or fecal incontinence. Patients should be evaluated for spinal/cervical cord compression prior to initiation of NAGLAZYME to establish a baseline and risk profile. Patients treated with NAGLAZYME should be regularly monitored for the development or progression of spinal/cervical cord compression and be given appropriate clinical care.

Adverse Reactions
During infusion, serious adverse reactions included laryngeal edema, apnea, pyrexia, urticaria, respiratory distress, angioedema, and anaphylactoid reaction; severe adverse reactions included urticaria, chest pain, rash, abdominal pain, dyspnea, apnea, laryngeal edema, and conjunctivitis. The most common adverse events (≥10%) observed in clinical trials in patients treated with NAGLAZYME were rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain and dyspnea. The most common adverse reactions requiring interventions are infusion-related reactions.

 

To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-888-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information with Boxed Warning for risk of anaphylaxis or visit www.Naglazyme.com.

INDICATION
NAGLAZYME® (galsulfase) is indicated for patients with mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity.