Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder, also known as classical homocystinuria (OMIM 236200). Homocysteine (Hcy) is a non-structural amino acid (AA) that is formed in the catabolic pathway for the essential AA, methionine (Met). CBS deficiency impairs the conversion of Hcy to cystathionine and leads to its accumulation.
Patients with CBS deficiency show a wide spectrum of severity and age at presentation. Some patients have a severe childhood-onset multisystem disease, whilst others are asymptomatic into adulthood. The main clinical features are dislocation of the optic lenses, osteoporosis and a ‘marfanoid’ habitus, learning difficulties and a predisposition to thromboembolism. Other causes of hyperhomocysteinemia include inborn errors of Hcy remethylation, vitamin deficiencies (especially B12), renal insufficiency and medication.
CBS is expressed predominantly in liver, pancreas, kidney and brain. Its catalytic domain binds heme and the cofactor pyridoxal 5′phosphate, in addition to its substrates; the regulatory domain binds SAM as an allosteric activator.