A 10-year-old boy evaluated for a deep vein thrombosis is noted to be tall with long thin limbs, genu valgum, pectus excavatum, and high-arched feet. He has downward and inward subluxation of both lenses and mild intellectual disability. Urine homocysteine is markedly elevated. Which enzyme deficiency causes this disorder?

• A Alpha-L-iduronidase
• B Methionine synthase reductase
• C Cystathionine beta-synthase ✓
• D Gamma-glutamyl transpeptidase

Explanation

Classic homocystinuria results from cystathionine beta-synthase deficiency, causing accumulation of homocysteine and methionine. The combination of marfanoid habitus, downward lens dislocation, thromboembolic events, and intellectual disability distinguishes it from Marfan syndrome, in which lens dislocation is upward and thrombosis does not occur. About half of patients respond biochemically to pharmacological doses of pyridoxine (vitamin C6). Alpha-L-iduronidase deficiency causes Hurler syndrome.

Reference: Nelson Textbook of Pediatrics, 22nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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