Reduced activity of cystathionine-synthase results in accumulation of homocysteine and methionine, interfering with collagen cross-linking, which is the cardinal feature of homocystinuria.
- Marfanoid appearance and arterial and venous thrombi
- There is a deficiency of cystathionine Beta-synthase
- This catalyses cystathionine formation from homocysteine.
- Homocysteine accumulates and dimerises to form homocysteine
- Venous thrombosis
- Arterial thrombotic/embolic disease, especially with severe hyperhomocysteinemia (total plasma homocysteine greater than 100 mol/L)
- Autosomal recessive
- Loss of function of the CBS gene for cystathionine Beta-synthase
- Learning difficulties, Marfanoid with tall build
- Arachnodactyly (spidery fingers), pectus excavatum, scoliosis
- Lens dislocation downwards
- Generalised osteoporosis
- Vascular thrombotic/embolic disease, e.g. MI before aged 30
- Spontaneous pneumothorax is reported in some adolescents
- Fair skin with coarse hair, osteoporosis, mental retardation (nearly 50%)
- Seizure disorder, marfanoid habitus, and increased thromboembolic risk.
- High arch palate, chest wall deformities
- Livedo reticularis, which is seen in homocystinuria due to the venous thrombosis in the small vessels of the skin, is not seen in Marfan's syndrome
- With Marfan's, the lens dislocates up, and in Homocystinuria, the lens dislocate downwards
- Increased level of homocysteine in the urine, which gives a positive urine cyanide-nitroprusside test.
- An amino acid screen of blood and urine shows elevated methionine and homocysteine levels.
- A skin biopsy with a fibroblast culture shows an abnormality of cystathionine Beta synthase
- A liver biopsy and enzyme assay show an abnormality of the enzyme cystathionine beta-synthase.
- Treat with high dose Pyridoxine (B6)and low methionine diet (however will not improve the mental retardation unless started in the neonatal period)