Clinical Presentation

Musculoskeletal manifestations1

Joint stiffness and contracture. The stiffness and contracture in MPS I/MPS II often resembles rheumatic conditions but has several distinguishing features: stiffness is not worse in the morning and is not exacerbated by rest or relieved by activity; the interphalangeal joints are usually affected and underlie a characteristic claw hand deformity that often results in impaired hand function; local and systemic signs of inflammation are absent; swollen appearance of joints is caused by bony enlargement rather than synovial effusion; articular abnormalities are unresponsive to steroids or other anti-inflammatory treatment. Radiographic changes characteristic of inflammatory arthritis, for example erosive bone lesions, joint space narrowing or joint effusions, do not occur in MPS.

Claw hand deformity in MPS I/MPS II

  • Trigger finger.
  • Dysostosis multiplex, a group of radiographic changes characteristic of MPS disorders. Skeletal abnormalities include:
    • flattened vertebral bodies
    • odontoid hypoplasia
    • thoracolumbar kyphosis
    • oar-shaped ribs
    • short thickened clavicles
    • large skull with thickened calvarium and J-shaped sella turcica
    • dysplastic femoral heads
    • flattened acetabula
    • hypoplasia of the inferior portions of the iliac bones with flared iliac wings
    • coxa valga
    • genu valgum deformities. Scoliosis, hip dysplasia, and genu valgum may develop.
  • Disproportionate short stature. This is characteristic in all but the most attenuated form of MPS I (Scheie syndrome), in which stature may be normal or near normal.2,3
  • Toe-walking, due to joint stiffness and contracture involving the ankles and Achilles tendons.1
  • Abnormal gait and impaired walking ability due to a combination of foot, hip and joint abnormalities, joint contracture, and genu valgum.1

Ocular manifestations

  • Discrete corneal lesions (only in MPS II), visible by slit-lamp examination, that do not affect vision. Some patients have bilateral pigmentary changes and the loss of field of vision.4
  • Corneal clouding (only in MPS I), which may result in loss of vision.5
  • Glaucoma (uncommon in MPS II).4,6

Gastrointestinal manifestations6,7

  • Hepatosplenomegaly, resulting in abdominal distention.
  • Inguinal and umbilical hernia

Respiratory manifestations4,5

  • Progressive airway obstruction, caused by narrowed and abnormally shaped trachea and bronchi, enlarged tongue, hypertrophic adenoids and tonsils, large epiglottis, frequent upper respiratory infections, recurrent pneumonia, and thick nasal and tracheal secretions. Sleep apnoea is a common complication.
  • Obstructive or restrictive lung disease, caused by a combination of skeletal abnormalities of the chest and spine and hepatosplenomegaly.8

Cardiovascular manifestations

  • Valvular disease can occur in all forms of MPS I and MPS II. Left-sided valvular disease causing regurgitation or stenosis is common in attenuated MPS I.5 In MPS II, valvular abnormalities are the most common cardiac manifestations; cardiomyopathy, abnormal heart frequency, congestive heart failure, arrhythmia and systemic hypertension are less common manifestations.9
  • Arrhythmia, cardiomyopathy, congestive heart failure, coronary artery disease, pulmonary and systemic hypertension, and cor pulmonale may develop in addition to valvular disease in patients with MPS I.
  • Left ventricular hypertrophy occurs in around half of all patients with MPS II.9

Dermatological manifestations

  • Skin may be thickened and inelastic in individuals with MPS II.4
  • Distinctive skin lesions described as skin-coloured papules are characteristic of MPS II, although there has been a report of similar lesions in a patient with MPS I.4,10

Auditory manifestations

  • Conductive and neurosensory deafness. Frequent ear infections, defective ossification in the middle ear, scarring of the tympanic membrane, or nerve damage may contribute hearing loss.4,5

Mouth and teeth4,5,11

  • Gum, tooth, and enamel abnormalities including irregularly or peg shaped teeth, frequent caries, dentigerous and gingival cysts, and hyperplastic and hypertrophic gingival tissue.

Facial dysmorphism2,4

  • Coarse facial features including broad nose with flared nostrils, prominent supraorbital ridges, large jowls, thick lips, and enlarged protruding tongue.
  • Large head circumference throughout life.

Neurological manifestations4,5

  • Global delay of developmental milestones such as ability to sit unsupported, ability to walk, and ability to speak (only in severe forms of MPS I/MPS II).
  • Cognitive impairment (only in severe forms of MPS I/MPS II).
  • Moderate-to-severe communicating hydrocephalus. Headache, vomiting or drowsiness are symptoms more commonly seen in MPS II. Abnormal eye movements and acute loss of vision tend to be the presenting features in MPS I.
  • Seizures are common in severe forms of MPS II and less common in attenuated forms of MPS II.12 Seizures may be subtle initially and appear as “staring” episodes. Seizures are not a feature of MPS I.13
  • Spinal cord compression, causing weakness in the lower extremities or abnormal gait (uncommon in severe MPS I).
  • Carpal tunnel syndrome that is commonly atypical in presentation (many young patients do not complain of numbness or pain).1

Behavioural disturbances

  • Hyperactive and aggression behaviour (severe MPS II only).4


  1. 1.Cimaz R, La Torre F. (2014) Mucopolysaccharidoses. Curr Rheumatol Rep 16(1): 389.
  2. 2.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. 3.Morishita K, Petty RE. (2011) Musculoskeletal manifestations of mucopolysaccharidoses. Rheumatology (Oxford) 50 Suppl 5: v19-25.
  4. 4.Martin R, Beck M, Eng C, et al. (2008) Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics 121(2): e377-386.
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  7. 7.Wraith JE, Beck M, Giugliani R, et al. (2008) Initial report from the Hunter Outcome Survey. Genet Med 10(7): 508-516.
  1. 8.Lin SP, Shih SC, Chuang CK, et al. (2014) Characterization of pulmonary function impairments in patients with mucopolysaccharidoses--changes with age and treatment. Pediatr Pulmonol 49(3): 277-284.
  2. 9.Kampmann C, Beck M, Morin I, Loehr JP. (2011) Prevalence and characterization of cardiac involvement in Hunter syndrome. J Pediatr 159(2): 327-331 e322.
  3. 10.Thappa DM, Singh A, Jaisankar TJ, Rao R, Ratnakar C. (1998) Pebbling of the skin: a marker of Hunter's syndrome. Pediatr Dermatol 15(5): 370-373.
  4. 11.Guven G, Cehreli ZC, Altun C, et al. (2008) Mucopolysaccharidosis type I (Hurler syndrome): oral and radiographic findings and ultrastructural/chemical features of enamel and dentin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(1): 72-78.
  5. 12.Muenzer J, Beck M, Eng CM, et al. (2009) Multidisciplinary management of Hunter syndrome. Pediatrics 124(6): e1228-1239.
  6. 13.Burton BK, Giugliani R. (2012) Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 171(4): 631-639.