Abstrakt
Cystathionine β-synthase (CBS) catalyses condensation of homocysteine and serine to cystathionine, and by alternative reactions also synthesis of hydrogen sulfide. CBS deficiency, an autosomal recessive trait with estimated worldwide frequency of 0.82-1.09 per 100 000 births, manifests usually by thromboembolism, and in severe forms also by lens dislocation, marfanoid features, osteoporosis and neuropsychiatric complications.
Laboratory findings include grossly elevated plasma total homocysteine and mildly to grossly elevated blood methionine, which is analysed in neonatal screening. CBS binds three cofactors: pyridoxal-5'-phosphate, an allosteric activator S-adenosylmethionine and haem with as-yet-unresolved function.
In the CBS gene, more than 160 different mutations have been described to date. Most of the mutations are missense yielding misfolded enzymes, which can potentially be rescued by chaperones.
CBS deficiency is efficiently treated by combination of large doses of pyridoxine, methionine-restricted diet and betaine; experimental enzyme replacement therapy is efficient in mouse models of disease.