Mucopolysaccharidosis Type I (Hurler / Scheie Syndrome)

Mucopolysaccharidosis type I (MPS I) is a rare, inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase. Without enough functional enzyme, complex sugar molecules called glycosaminoglycans (GAGs) accumulate progressively inside cells throughout the body, gradually affecting the skeleton, joints, heart valves, cornea, airway, liver, spleen, and in the most severe form, the brain.

MPS I spans a wide clinical spectrum. The severe form, historically called Hurler syndrome, usually presents in infancy with coarsening facial features, hepatosplenomegaly, and developmental regression. Attenuated forms, including Hurler-Scheie and Scheie syndrome, present later in childhood or even adulthood and primarily affect the joints, heart, and cornea while sparing intellectual development.

Because MPS I is progressive, early diagnosis dramatically changes what treatment options remain available, particularly for the severe infantile form, where hematopoietic stem cell transplantation is most effective when performed before significant disease progression.

MPS I is classified along a clinical spectrum based on age of onset, rate of progression, and degree of central nervous system involvement, rather than as fully distinct diseases.

Symptom presentation depends heavily on where a person falls on the MPS I severity spectrum, but most individuals develop a combination of skeletal, cardiac, respiratory, and ocular findings over time.

MPS I is caused by mutations in the IDUA gene, which provides instructions for producing alpha-L-iduronidase, an enzyme responsible for breaking down specific glycosaminoglycans inside lysosomes. When enzyme activity is absent or severely reduced, these molecules accumulate progressively in cells throughout the body.

Diagnosis combines clinical suspicion based on physical findings with biochemical and genetic confirmation.

MPS I does not use a tumor-staging framework. Instead, clinicians classify disease severity along a phenotypic spectrum that guides treatment urgency and selection, particularly the decision around stem cell transplantation.

Treatment for MPS I combines disease-modifying therapy aimed at reducing GAG accumulation with ongoing multidisciplinary supportive management of affected organ systems.

Beyond standard enzyme replacement therapy, several approaches are expanding what is possible for individuals with MPS I, particularly for central nervous system involvement that intravenous enzyme replacement does not adequately address.

Biochemical and genetic markers are central to confirming diagnosis, classifying severity, and monitoring response to therapy in MPS I.

Because MPS I management decisions, especially around transplant timing, can be time-sensitive and complex, a specialist second opinion is often valuable at key decision points.

Outcomes in MPS I vary substantially with phenotype and how early disease-modifying therapy begins. Without treatment, the severe form is associated with significant early-life morbidity and shortened life expectancy, while attenuated disease can be compatible with a longer lifespan, particularly with consistent enzyme replacement and supportive care.

Living with MPS I involves ongoing coordination across multiple specialists, and supportive measures meaningfully improve daily function and quality of life.