CBS

Homocystinuria

More than 150 mutations that cause homocystinuria have been identified in the CBS gene. Most of these mutations change single amino acids in cystathionine beta-synthase. The most common mutation substitutes the amino acid threonine for the amino acid isoleucine at position 278 in the enzyme (written as Ile278Thr or I278T). Another common mutation, which is the most frequent cause of homocystinuria in the Irish population, replaces the amino acid glycine with the amino acid serine at position 307 (written as Gly307Ser or G307S). These mutations disrupt the normal function of cystathionine beta-synthase. As a result, homocysteine and other potentially toxic compounds build up in the blood, and homocysteine is excreted in urine. Researchers have not determined how excess homocysteine leads to the signs and symptoms of homocystinuria.