Related Subjects:
|Osteoporosis
|Autosomal Dominant
|Autosomal Recessive
|X Linked Recessive
๐งฌ Homocystinuria is caused by reduced activity of cystathionine ฮฒ-synthase (CBS), leading to accumulation of homocysteine and methionine. This disrupts collagen cross-linking and predisposes to vascular thrombosis โ the cardinal feature.
โน๏ธ About
- ๐ค Marfanoid habitus with tall build and long fingers
- โ ๏ธ High risk of arterial & venous thromboembolic events (MI, stroke, DVT)
๐งช Aetiology
- Deficiency of Cystathionine ฮฒ-synthase (CBS enzyme)
- Homocysteine โ accumulates and dimerises
- Results in vascular injury & thrombosis (often severe if plasma homocysteine >100 ยตmol/L)
๐ฌ Biochemistry
๐งฌ Genetics
- Inheritance: Autosomal recessive
- Mutation: CBS gene
๐ฉบ Clinical Features
- ๐ Learning difficulties / developmental delay
- ๐ Tall, thin, marfanoid build with arachnodactyly, scoliosis, pectus deformities
- ๐๏ธ Lens dislocation downwards (cf. Marfanโs = upwards)
- ๐ฆด Generalised osteoporosis, fractures
- โค๏ธ Early vascular events: MI, stroke, DVT before age 30
- ๐ง Seizures, intellectual disability (โ50%)
- ๐ธ Fair skin, coarse hair (reduced melanin pathway)
- ๐ซ Rare: spontaneous pneumothorax
- ๐ Livedo reticularis (from venous thrombosis in dermal vessels)
๐ Differential
- Marfanโs syndrome: upward lens dislocation, no thrombotic risk
๐งพ Investigations
- ๐ง Urine: positive cyanide-nitroprusside test (โ homocysteine)
- ๐ฉธ Plasma/urine amino acid screen: โ homocysteine & methionine
- ๐งซ Fibroblast culture or liver biopsy: abnormal CBS enzyme
๐ Management
- ๐ High-dose Pyridoxine (Vitamin B6) (cofactor for CBS) โ responsive in some cases
- ๐ฅ Low-methionine diet + betaine, folate, B12 supplementation (support remethylation pathways)
- ๐ผ Early treatment essential to prevent intellectual disability
๐ฉบ Case 1 โ Child with Developmental Delay
A 6-year-old boy is brought with learning difficulties, clumsiness, and tall, thin build with long fingers resembling Marfanโs habitus. He has fair hair and blue eyes. Ophthalmology finds downward lens dislocation (ectopia lentis). Blood tests show elevated plasma homocysteine. Management: ๐ High-dose pyridoxine (B6) in responsive patients, plus folate and B12 supplementation. Restrict methionine intake, supplement cysteine. Avoid: โ Missing diagnosis by assuming Marfanโs; avoid unmonitored protein-rich diets that worsen methionine load.
๐ฉบ Case 2 โ Teen with Thromboembolism
A 16-year-old girl presents with sudden left leg swelling and pain. Doppler ultrasound shows extensive DVT. She has mild learning difficulties and a history of lens surgery for dislocation. Labs: markedly raised homocysteine levels confirming homocystinuria. Management: ๐ฉบ Anticoagulation for thrombosis, long-term homocysteine-lowering therapy (pyridoxine, folate, B12, betaine). Genetic counselling.
Avoid: โ Oestrogen-containing contraceptives (increase thrombotic risk). Avoid prolonged immobilisation without prophylaxis.
