Definition
- Autosomal recessive disorder of methionine metabolism with accumulation of homocysteine
Aetiology
- Cystathionine beta synthase deficiency in most cases
Clinical Features
- Marfanoid habitus with tall stature and arachnodactyly
- Lens dislocation downward, opposite to Marfan syndrome
- Intellectual disability and seizures
- Venous and arterial thrombosis
- Joint stiffness, unlike the laxity of Marfan syndrome
- Osteoporosis, absent in Marfan syndrome
- Scoliosis
- Flared distal femur
- Tibial bowing
- Enlarged carpal bones
- Biconcave codfish vertebrae
Investigations
- Raised plasma total homocysteine
- Raised blood methionine
- Positive cyanide nitroprusside urine screen
- Newborn screening detects many cases
Differential Diagnosis
- Marfan syndrome
- Loeys-Dietz syndrome
- Stickler syndrome
Management
- Pyridoxine trial, as some patients are responsive
- Methionine restricted diet
- Betaine, folate and vitamin B12
- Bisphosphonates for osteoporosis
- Bracing or fusion for scoliosis
Complications
- Thromboembolism after surgery and anaesthesia
- Perioperative hydration, early mobilisation and thromboprophylaxis
- Avoid nitrous oxide, which worsens hyperhomocysteinaemia
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.