Clinical Information

The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate, also known as glycosaminoglycans (GAG) or mucopolysaccharides. Accumulation of GAG in lysosomes interferes with normal functioning of cells, tissues, and organs. There are 11 known disorders that involve the accumulation of GAG. MPS disorders involve multiple organ systems and are characterized by coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature, and skeletal abnormalities.

Mucopolysaccharidosis 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 GAG dermatan sulfate and heparan sulfate (see MPSSC / Mucopolysaccharides Screen, Random, Urine; MPSWB / Mucopolysaccharides, Blood). Reduced or absent activity of alpha L-iduronidase can confirm a diagnosis of MPS I; however, enzymatic testing is not reliable for carrier detection. Molecular sequence analysis of the IDUA gene allows for detection of a disease-causing variant in affected individuals and subsequent carrier detection in relatives (see MPS1Z / Hurler Syndrome, Full Gene Analysis, Varies). To date, a clear genotype-phenotype correlation has not been established.