Homocystinuria — RACP Adult Medicine MCQ

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HardHaematologyHomocystinuriaRACP Adult Medicine

A 45-year-old man presents with recurrent deep vein thrombosis. Thrombophilia screening reveals homocysteine of 55 µmol/L (markedly elevated). His vitamin B12 and folate levels are normal. What is the underlying cause?

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Correct answer: D — Cystathionine beta-synthase deficiency (homocystinuria)

Markedly elevated homocysteine (>50 µmol/L) with normal B12 and folate should raise suspicion for an inherited disorder of homocysteine metabolism, most commonly cystathionine beta-synthase (CBS) deficiency (classic homocystinuria). This autosomal recessive condition presents with marfanoid habitus, lens subluxation (downward – unlike Marfan which is upward), intellectual disability, and venous/arterial thromboembolism. MTHFR C677T homozygosity causes only mild elevation (15–30 µmol/L). Treatment includes high-dose pyridoxine (B6) for responsive patients, betaine, folate, and B12.

Reference: eTG – 2025 – Haematology; ACMG – 2020 – Homocystinuria Guidelines