A 6-month-old boy presents with progressive macrocephaly, coarse facial features, hepatosplenomegaly, and corneal clouding. Urinary glycosaminoglycans (heparan sulfate and dermatan sulfate) are markedly elevated. Enzyme assay confirms alpha-L-iduronidase deficiency. What is this diagnosis and what is the MAJOR distinguishing feature between Hurler (MPS IH) and Scheie (MPS IS) syndrome?

• A Both caused by IDUA deficiency but Hurler is severe with CNS involvement; Scheie is attenuated with normal intelligence ✓
• B Hurler and Scheie have different enzyme deficiencies — IDUA vs. IDS
• C Scheie lacks corneal clouding; Hurler has corneal clouding
• D Hurler affects males only due to X-linked inheritance; Scheie is autosomal recessive

Explanation

Both Hurler syndrome (MPS IH) and Scheie syndrome (MPS IS) are caused by deficiency of alpha-L-iduronidase (IDUA gene, chromosome 4p16.3), an enzyme that degrades heparan and dermatan sulfate. They represent phenotypic extremes of the same enzyme deficiency: Hurler (severe) causes progressive CNS deterioration, intellectual disability, cardiomyopathy, and early death; Scheie (mild/attenuated) presents with normal intelligence, corneal clouding, and joint stiffness, surviving into adulthood. Hunter syndrome (MPS II) is the X-linked form caused by iduronate-2-sulfatase (IDS) deficiency, predominantly affecting males. Both Hurler and Scheie have corneal clouding.

Reference: Ghai Essential Pediatrics, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.