Mucopolysaccharidosis type 1

Mucopolysaccharidosis type 1 (MPS I) is a rare inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase (IDUA), which is needed to break down glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate. When this enzyme is absent or deficient, these complex sugar molecules accumulate progressively in cells and tissues throughout the body, leading to widespread organ damage. MPS I encompasses a spectrum of clinical severity historically divided into three subtypes: Hurler syndrome (MPS I-H, the most severe form), Hurler-Scheie syndrome (MPS I-H/S, an intermediate form), and Scheie syndrome (MPS I-S, the attenuated form). Today, clinicians often classify MPS I as either severe or attenuated. The disease affects multiple body systems. Key clinical features include coarse facial features, skeletal abnormalities (dysostosis multiplex), joint stiffness and contractures, hepatosplenomegaly (enlarged liver and spleen), corneal clouding, hearing loss, cardiac valve disease, and upper airway obstruction. In the severe (Hurler) form, progressive cognitive decline and developmental regression typically begin in the first two years of life, and without treatment, life expectancy is often limited to the first decade. Attenuated forms present later with variable severity; intelligence is usually preserved, but progressive somatic disease can cause significant disability. Two main treatment approaches are available. Enzyme replacement therapy (ERT) with laronidase (Aldurazyme) provides recombinant alpha-L-iduronidase intravenously and can improve many somatic symptoms, though it does not cross the blood-brain barrier effectively. For severe MPS I diagnosed early, hematopoietic stem cell transplantation (HSCT) is the standard of care, as it can preserve neurocognitive function if performed before significant neurological damage has occurred, ideally before age two. Newborn screening programs for MPS I have been implemented in several countries to enable early diagnosis and timely intervention. Supportive care including orthopedic, cardiac, ophthalmologic, and respiratory management remains essential for all patients.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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