Expansion
Cystathionine beta synthase deficiency, resembling Marfan syndrome with thrombosis
Expansion
Defect: usually cystathionine beta synthase, which requires vitamin B6. It normally converts homocysteine to cystathionine, so homocysteine accumulates and cysteine becomes essential.
Features
- Marfanoid habitus: tall, long limbs, arachnodactyly, pectus deformity
- Lens dislocation, downwards (ectopia lentis)
- Intellectual disability and psychiatric disturbance
- Thrombosis: arterial and venous, the main cause of death, from endothelial damage
- Osteoporosis
Distinguishing from Marfan syndrome: Marfan is autosomal dominant with upward lens dislocation, normal intelligence, no thrombotic tendency, and aortic root dilatation as the main risk. Homocystinuria is autosomal recessive.
Treatment
- About half are pyridoxine (B6) responsive, which should always be tested
- Methionine-restricted diet with cysteine supplementation
- Betaine, which provides an alternative remethylation route
- Folate and B12 to support remethylation
Milder elevations of homocysteine, from folate, B12 or B6 deficiency or the MTHFR variant, are common and are an independent cardiovascular risk factor.