Clinical Presentation

Patients with MPS I face a multitude of serious and often debilitating multisystemic manifestations

In MPS I, the IDUA enzyme is deficient or essentially absent, causing GAG substratesa to accumulate in cells, leading to progressive damage to tissues and organs.1-7

Some common manifestations include4-7:

Signs & Symptoms of MPS 1 in different body parts of a human being
  • The GAGs that accumulate in MPS I are dermatan sulfate and heparan sulfate.1
  • Scheie form has no cognitive impairment.5

Examples of disease progression include5-7:

    • Common in patients with MPS I
    • Cardiomyopathy and endocardial fibroelastosis can occur in children with severe MPS I
    • Coronary artery disease can lead to death
    • Patients with attenuated form may develop aortic or mitral valve disease
      • may have slowly progressive valvular heart disease for years
      • may need mitral or aortic valve replacement as early as in their teens and twenties5
    • Can occur early in life, by about 6 months of age
    • Bone abnormalities are common, some of them are:
      • hip abnormalities, ovoid vertebrae, and widening of the ribs
      • a poorly formed pelvis, a gibbus deformity of the back, and shortened phalanges 
    • Progressive skeletal dysplasia can occur in all types of MPS I
    • Joint stiffness is common in all forms of MPS I5
    • Apparent in the severe form of MPS I—starting at 12–24 months of age, typically with a maximum functional age of 2-4 years. Then followed by slowed development and progressive regression in developmental skills until death.
    • Mildly affected patients with the attenuated form generally have unaffected cognition5
    • Physical appearance of some infants with severe and moderate-to-severe symptoms of MPS I may appear unaffected at birth, but as early as 3 months of age, parents may notice changes in the child’s facial features.6
    • Characteristic facial features of these patients include:
      • short noses, flat faces, prominent foreheads, and large heads, which tend to be longer than normal from front to back (scaphocephaly)7
    • The overall appearance in attenuated form of MPS I is extremely variable
      • adults are often stocky in build and their trunks shorter than their limbs
      • neck may be short and stiff  
      • unremarkable facial appearance

This is not meant to be a comprehensive list of all manifestations associated with MPS I.

MPS I can present with a wide spectrum of signs and symptoms

It is important to identify the common manifestations across the spectrum of MPS I to piece together the diagnosis of this potentially fatal disease.4

Common clinical manifestations in severe and attenuated
MPS I5,6,8,9

Clinical manifestations based on severity of symptoms in severe and attenuated patients

Joint pain and joint contractures are common among patients with attenuated MPS I

Evolving joint pain and joint contractures in the absence of inflammation should always raise suspicion of an MPS disorder.9

80% share

>80% of patients with attenuated MPS I have joint contractures and are likely to see a rheumatologist†9

†According to MPS I Registry Data.

GAG, glycosaminoglycan; IDUA, α-L-iduronidase; MPS, mucopolysaccharidosis

References: 1. de Ru MH, Boelens JJ, Das AM, et al. Orphanet J Rare Dis. 2011;6(55):1-9. 2. Wraith JE, Clarke LA, Beck M, et al. J Pediatr. 2004;144(5):581-588. 3. D’Aco K, Underhill L, Rangachari L, et al. Eur J Pediatr. 2012;171(6):911-919. 4. Beck M, Arn P, Giugliani R, et al. Genet Med. 2014;16(10):759-765. 5. Neufeld EF, Muenzer J. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 4. 8th ed. McGraw-Hill; 2001:2465-2494. Accessed March 02, 2022. 6. Cleary MA, Wraith JE. Acta Paediatr. 1995;84(3):337-339. 7. Scheie HG, Hambrick GW, Barness LA. Am J Ophthalmol. 1962;53:753-769. 8. Wraith JE. Expert Opin Pharmacother. 2005;6(3):489-506. 9. Cimaz R, Coppa GV, Kone-Paut I, et al. Pediatr Rheumatol Online J. 2009;7:18.

MAT-US-2205116-v1.0-10/2022 Last Updated: October 2022