Clinical Information

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by reduced or absent activity of the enzyme alpha-L-iduronidase due to variants in the IDUA gene. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypes categorized into 3 syndromes: Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S). Because these syndromes cannot be distinguished biochemically, they are also referred to as MPS I and attenuated MPS I.

Clinical features and severity of symptoms of MPS I are variable, ranging from severe disease to an attenuated form that generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, intellectual disabilities or learning difficulties, and cardiac valvular disease. The incidence of MPS I is approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

Individuals with MPS I typically demonstrate elevated levels of the glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate (see MPSQU / Mucopolysaccharides Quantitative, Random, Urine; MPSBS / Mucopolysaccharides, Blood Spot), as well as elevated levels of GAG fragments known as endogenous disaccharide biomarkers that are specific to the deficiency of alpha-L-iduronidase. Reduced or absent activity of alpha L-iduronidase (see IDUAW / Alpha-L-Iduronidase, Leukocytes) can confirm a diagnosis of MPS I but may also be deficient in unaffected individuals who are carriers or with pseudodeficiency. Molecular sequence analysis of the IDUA gene allows for detection of disease-causing variants in affected individuals and subsequent carrier detection in relatives (see MPS1Z / Hurler Syndrome, Full Gene Analysis, Varies).