FFinalistSouthampton · 2027
Endocrine
AKT · Endocrine/Lipids, metabolic & inheritedlow yield

Homocystinuria

Autosomal-recessive cystathionine β-synthase deficiency

Overview

Autosomal-recessive deficiency of cystathionine β-synthase, causing homocysteine accumulation. A Marfan-like phenotype (tall, long limbs, lens dislocation) but with intellectual disability and, crucially, a strong thrombotic tendency. The lens dislocates DOWNWARD (vs upward in Marfan). Treated with pyridoxine (B6), diet and anti-thrombotic measures.

Recognise

  • Marfanoid habitus (tall, arachnodactyly, pectus) WITH intellectual disability and ectopia lentis (lens dislocation — typically DOWNWARD)
  • Thromboembolism (arterial and venous — a major cause of morbidity/death), osteoporosis, fair complexion
  • Raised plasma/urine homocysteine

Red flags

  • Thromboembolic events (stroke, DVT/PE) — especially around surgery/anaesthesia
  • Lens dislocation/glaucoma

Differentials & how to tell them apart

Marfan syndromelens dislocates UPWARD, NORMAL intelligence, aortic root dilatation, no thrombosis/homocysteine rise
Other causes of ectopia lentistrauma, Weill-Marchesani — clinical/biochemical context

Investigations

Plasma/urine homocysteine (raised), methionine; enzyme/genetic testing; ophthalmology (lens); newborn screening in some regions.

Management

Pyridoxine (B6); methionine-restricted diet ± betaine; thrombosis prophylaxis

  1. 1Confirm raised homocysteine. Trial pyridoxine (B6) — many respond; add methionine-restricted diet, betaine, folate/B12 for non-responders. Reduce thrombotic risk.Gate: Distinguish from MARFAN (downward vs upward lens dislocation, intellectual disability, and the THROMBOTIC tendency) — homocystinuria needs anti-thrombotic care and B6, not just connective-tissue management
  2. 2Lifelong biochemical control and thrombosis prevention (especially perioperatively); ophthalmology; genetic counselling.
Pyridoxine (vitamin B6) — first-line — many are B6-responsive (lowers homocysteine)
Methionine-restricted diet + betaine + folate/B12 — for non-responders/adjunct
Antithrombotic measures — reduce the high thrombotic risk, especially perioperatively

Key points

Marfanoid + intellectual disability + DOWNWARD lens dislocation + thrombosis = homocystinuria (not Marfan). B6-responsive in many. The thrombotic risk is the killer.

Monitor & prognosis

Homocysteine; thrombotic events; lens/eye.

Improved with treatment; thrombosis is the main risk.

Source: BIMDG; StatPearls