A 3-year-old boy with coarse facial features, corneal clouding, hepatosplenomegaly, and skeletal deformities (gibbus deformity) is found to have elevated urinary dermatan sulfate and heparan sulfate. Enzyme assay confirms alpha-L-iduronidase deficiency. Which of the following correctly distinguishes Hurler syndrome (MPS I-H) from Scheie syndrome (MPS I-S)?

• A Scheie syndrome is caused by a different enzyme deficiency than Hurler syndrome
• B Scheie syndrome lacks corneal clouding, which is present in Hurler
• C Hurler syndrome has predominant heparan sulfate excretion, Scheie predominantly dermatan sulfate
• D Both are due to alpha-L-iduronidase deficiency; Hurler has severe CNS involvement with early death, Scheie has near-normal intelligence with primarily somatic disease ✓

Explanation

Both Hurler (MPS I-H) and Scheie (MPS I-S) syndromes result from mutations in the IDUA gene encoding alpha-L-iduronidase, with the same biochemical pathway affected. They represent a clinical spectrum based on residual enzyme activity: Hurler syndrome (severe end) presents in infancy with progressive intellectual deterioration, corneal clouding, severe skeletal dysostosis, organomegaly, and death usually by age 10; Scheie syndrome (attenuated end) presents with corneal clouding, stiff joints, carpal tunnel syndrome, and aortic valve disease but near-normal intelligence and lifespan. Both excrete dermatan and heparan sulfates. An intermediate form, Hurler-Scheie, also exists.

Reference: Ghai Essential Pediatrics, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.