Mucopolysaccharidosis (MPS) disorders are a group of inherited enzyme deficiencies with heterogeneous presentation and variable disease progression that are suspected to affect 1 in 22,500 live births worldwide.1,2
Similar clinical manifestations and rates of progression are seen across MPS disorders. The images below illustrate patterns of MPS disease progression as seen in a patient with MPS VI.
Variable disease progression in patients with MPS VI
All patients, regardless of initial presentation, are at risk for end-organ damage.
Perceived disease rarity, variability in disease progression and presentation and the myriad of nonspecific symptoms associated with MPS make diagnosis challenging. Time to diagnosis from first symptom manifestation can range from six months to decades.3
Time to diagnosis in a series of patients with slowly progressing MPS VI4
In a small group of patients with MPS VI, median delay in diagnosis was found to be 17.5 years. Common among these patients was the lack of classic dysostosis multiplex.
Early diagnosis can enable improved patient outcomes through access to disease-specific management and enzyme replacement therapy (ERT).3,5–8
For many MPS disorders, there is an ERT either already available or in development. The best way to diagnose MPS and, in turn, initiate treatment, is to refer any patient you suspect to a geneticist or metabolic centre familiar with testing for it.9
A constellation of suggestive findings is especially significant, but the absence of a particular finding or characteristic does not necessarily rule out an MPS diagnosis.10
When you see any number or pattern of signs that span multiple body systems and are indicative of MPS, don’t delay; refer to a geneticist or metabolic specialist.
Symptomatology for MPS:
Overt symptoms are those that can be observed during any routine office visit or physical examination. Investigate the key visual features of MPS that are listed below.
Adapted from Harmatz, Mol Genet Metab, 2013.
Abbreviation: ENT, Ear, Nose and Throat.
a25% of patients with Morquio A are classified as nonclassical.
bPercentages reflect prevalence of symptoms in 325 patients as reported in the Morquio A Clinical Assessment Program (MorCAP) study.
cThe range indicated refers to the incidence of cardiac valve regurgitation in adult patients (n=69; 28% mitral, 32% tricuspid, 39% aortic).
dThe range indicated refers to the incidence of reported spinal abnormalities (65% odontoid dysplasia, 49% cervical spine instability).
Slower walking speed, reduced cadence and lower than average stride length should trigger your suspicion of MPS.28
The chart below, representative of the growth trajectory that is typical of individuals with MPS, is taken from a cohort of 326 patients with Morquio A who participated in The International Morquio A registry.13
Growth trajectory in patients with Morquio A (MPS IVA)13,a
Boys growth curve in cm (n=167)
Average: 122.5 cm (over 18 years old, n=45)
Girls growth curve in cm (n=145)
Average: 117 cm (over 18 years old, n=62)
Adapted from Montaño, J Inherit Metab Dis, 2007.
Abbreviation: CDC, Centers for Disease Control and Prevention.
aWeight-for-age (kg) in patients with Morquio A (0 – 20 years) compared with normal growth chart from the CDC. These data correspond to all the participating patients who have data for the parameter. The data trend line and the 5th, 10th, 25th and 50th centile values for CDC standard weight curve are depicted.
Young patients who fall off the growth curve should raise your suspicion of MPS.
MPS disorders can present in any number of ways, often with a cluster of seemingly unrelated multisystemic symptoms. However, isolated symptoms also merit referral to a geneticist or metabolic centre.3,9
Surgical need is high among patients with MPS. Representative of this need, >70% of patients ≥5 years participating in MorCAP, a natural history study, had at least one surgical procedure.27
Common surgical procedures for MPS as seen in the Morquio A population27,a
Adapted from Harmatz, Mol Genet Metab, 2013.
aIncidence of surgical procedures in patients (n=325) participating in the MorCAP study.
Presentation and disease progression are unpredictable, multisystemic and variable across and within MPS disorders, making diagnosis challenging.3
Delayed diagnosis is common and it can have devastating consequences for your patients. Early identification of signs and symptoms across systems can be critical to early and accurate diagnosis.3,7,8 Become familiar with the diverse signs and symptoms of MPS that may present in your department.
As MPS treatment can have a life-changing impact, early and accurate diagnosis is critical.8,29 If there is any suspicion of MPS, consider referring to a geneticist or local metabolic centre.3
MPS presents as a diverse array of signs and symptoms, leading to a long list of potential misdiagnoses.8 Most common misdiagnoses include spondyloepiphyseal dysplasia congenita (SED), multiple epiphyseal dysplasia (MED), and Legg-Calvé-Perthes disease.14
A review of medical records of presenting signs and symptoms in 18 patients with Morquio A identified several misdiagnoses and other clinical diagnoses, shown in the list below.
Commonly misdiagnosed conditions prior to Morquio A diagnosis30
Adapted from Bhattacharaya, Orphanet J Rare Dis, 2014.
Similarly, as the table below describes, an analysis of 18 patients with MPS VI conducted by managing physicians identified common misdiagnoses associated with this subtype.
Reported misdiagnoses in a cohort of 18 patients with MPS VI31
The advancement of specific treatments for MPS highlights the importance of early intervention and referral of patients with suspected SED, MED, or Legg-Calvé-Perthes disease to a geneticist or metabolic centre.3,14,29
Adapted from Hendriksz, Br J Hosp Med (Lond), 2011.
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