Identifying MPS I and MPS II

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MPS I and MPS II affect multiple organ systems, resulting in a wide range of often non-specific, seemingly unrelated signs and symptoms that make recognition of the disorders challenging in clinical practice.

In combination with the heterogeneity of disease progression, this means that many patients typically present to a wide range of specialists.1

When to suspect MPS I/MPS II

Signs and symptoms of MPS I/MPS II can be difficult to identify as they may overlap with common childhood complaints. A cluster of common signs and symptoms of MPS I/MPS II, listed in the table below, should raise suspicion of an MPS disorder.2 In particular, coarse facial features are highly suggestive of MPS I/MPS II and are often the first sign detected by physicians during examination for other issues.3

Early signs and symptoms of MPS I/MPS II1,2,4,5

Coarse facial features (may be subtle in attenuated phenotypes)
Recurrent respiratory infections
Chronic rhinorrhea
Upper airway restriction/noisy breathing/snoring
Recurrent otitis media
Hearing loss
Heart murmur
Umbilical and inguinal hernia
Recurrent watery diarrhoea
Joint stiffness
Developmental delay and/or speech delay (in severe phenotypes only)
Carpal tunnel syndrome

The same somatic manifestations occur in all forms of MPS I and MPS II, but may be more subtle in attenuated phenotypes and therefore harder to recognise.2 Patients with attenuated disease are most likely to present to rheumatologists or orthopaedic surgeons with musculoskeletal complaints.5

Carpal tunnel syndrome (CTS), which is uncommon in paediatric patients, should raise suspicion of an MPS. MPS disorders are a frequent cause of CTS in childhood, although verbal limitations or cognitive impairment may make it difficult to identify.5

Disproportionate short stature is characteristic of MPS I and MPS II but may not be apparent at the time of diagnosis. Affected children may be larger than normal at birth. Slowing of growth usually begins after an initial period of accelerated growth in first 1-3 years of life.6,7 Individuals with the mildest form of MPS I (Scheie syndrome) may be of normal stature.7

Surgical history as a ‘red flag’ for MPS I/MPS II 

Surgical history can play an important role in identifying MPS I and MPS II. The majority of patients with MPS I/MPS II have a history of repeated surgical interventions at a young age, often before diagnosis. The most common surgical interventions are myringotomies and related procedures, hernia repair, adenoidectomy/tonsillectomy, and carpal-tunnel release. A history of such procedures should raise suspicion of MPS I/MPS II and prompt further examination and diagnostic testing.8,9

Surgeries most frequently performed in patients with MPS I before diagnosis

Adapted Figure 7 from Arn et al., J Pediatr 2009;154:859-64

The above graph shows the surgeries most frequently performed before diagnosis, by the number of surgeries overall, in patients with any form of MPS I enrolled in the MPS I Registry. “Other” denotes all surgeries not represented in any other category and includes appendectomy, cholecystectomy, pacemaker placement, and patent ductus arteriosus. Image source: Arn et al., J Pediatr 2009;154:859-64.

How to distinguish between MPS I and MPS II

It can be difficult to recognise a specific MPS subtype based on clinical presentation alone. This is because MPS I and MPS II share many clinical features (see Clinical Presentation) and each may appear in severe or attenuated forms. Although there are some distinguishing features, summarised in the table below, they are not present in all patients with a specific type of MPS.2

Clinical features specific to MPS I and MPS II

Characteristic MPS I MPS II
Corneal clouding + -
‘Pebbly’ skin lesions - (rare exceptions) +
Behavioural problems (hyperactivity, aggression) - +
Seizures - +

Family history can help identify the type of MPS, but it should be noted that past family diagnoses may not be reliable. This is because in the past, MPS I and MPS II were diagnosed clinically and were not recognised as distinct diseases (see History). Therefore, a family history of MPS I or Hurler syndrome should not exclude testing for MPS II and vice versa.2

When an MPS disorder is suspected, measurement of urinary GAG concentration and enzyme activity confirms diagnosis and the type of MPS (see Testing and Diagnosis).10


  1. 1.Scarpa M, Almassy Z, Beck M, et al. (2011) Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis 6: 72.
  2. 2.Burton BK, Giugliani R. (2012) Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 171(4): 631-639.
  3. 3.Martin R, Beck M, Eng C, et al. (2008) Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics 121(2): e377-386.
  4. 4.Muenzer J, Wraith JE, Clarke LA, International Consensus Panel on M, Treatment of Mucopolysaccharidosis I. (2009) Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 123(1): 19-29.
  5. 5.Cimaz R, La Torre F. (2014) Mucopolysaccharidoses. Curr Rheumatol Rep 16(1): 389.
  1. 6.Rozdzynska A, Tylki-Szymanska A, Jurecka A, Cieslik J. (2011) Growth pattern and growth prediction of body height in children with mucopolysaccharidosis type II. Acta Paediatr 100(3): 456-460.
  2. 7.Neufeld EF, Muenzer J. The Mucopolysaccharidoses In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, et al., editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2014.
  3. 8.Mendelsohn NJ, Harmatz P, Bodamer O, et al. (2010) Importance of surgical history in diagnosing mucopolysaccharidosis type II (Hunter syndrome): data from the Hunter Outcome Survey. Genet Med 12(12): 816-822.
  4. 9.Arn P, Wraith JE, Underhill L. (2009) Characterization of surgical procedures in patients with mucopolysaccharidosis type I: findings from the MPS I Registry. J Pediatr 154(6): 859-864 e853.
  5. 10.Muenzer J. (2011) Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 50 Suppl 5: v4-12.