A 14-year-old tall thin boy presents with sudden onset of chest pain and hemiparesis. Examination shows a high-arched palate, pectus excavatum, long limbs, and downward-inward displacement of the lens. Plasma total homocysteine is markedly elevated. What is the underlying enzyme defect?

• A Alpha-L-iduronidase deficiency
• B Fibrillin-1 mutation
• C Cystathionine beta-synthase deficiency ✓
• D Lysyl oxidase deficiency

Explanation

Classical homocystinuria due to cystathionine beta-synthase deficiency produces a marfanoid habitus, osteoporosis, intellectual disability, thromboembolic events, and ectopia lentis displaced downward and inward. The lens direction is the key discriminator from Marfan syndrome, where fibrillin-1 mutation displaces the lens upward and outward, and patients have normal homocysteine. Thrombosis of cerebral vessels explains the stroke presentation. Many patients respond to pyridoxine supplementation.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.