Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android


  • The complete transcription unit of MAT1A, the gene encoding the catalytic subunit of the two isozymes of methionine adenosyltransferase (MAT I and MAT III) expressed solely in nonfetal mammalian liver, has recently been characterized. It spans approximately 20 kbp and contains nine exons. Forty-eight patients with isolated hypermethioninemia have been shown to have deficiencies of the combined activity of these isozymes (MAT I/III deficiency). Most were ascertained during routine screening of newborns for hypermethioninemia or family screening. Seventeen mutations in MAT1A have been identified in these patients. Most patients have some residual activity of MAT I/III and are clinically well, but a few with complete MAT I/III deficiency have developed demyelination of the brain. MAT activities in tissues other than liver are normal, consistent with the functioning of the MAT isozyme(s) encoded by the separate gene, MAT2A. The residual activity of MAT in liver, the normal activities in nonhepatic tissues, and the high tissue concentrations of methionine together provide for synthesis by these individuals of virtually normal amounts of S-adenosylmethionine (AdoMet).

  • Cystathionine β-synthase (CBS) deficiency is the most frequently encountered cause of homocystinuria. In addition to Hcy, methionine and a variety of other metabolites of homocysteine accumulate in the body or are excreted in the urine of such patients. More than 600 cases of proven or presumptive CBS deficiency have been studied. Dislocation of the optic lens, osteoporosis, thinning and lengthening of the long bones, mental retardation, and thromboembolism affecting large and small arteries and veins are the most common clinical features. Affected patients vary widely in the extent to which they manifest these abnormalities or the rate at which they become apparent.

  • CBS deficiency is inherited as an autosomal recessive trait, but available evidence suggests considerable genetic heterogeneity. Some patients have small residual activities of CBS, whereas others have no such activities detected by even the most sensitive methods. Pyridoxine-responsive individuals generally have milder, or more slowly developing, manifestations than do those not responsive to pyridoxine.

  • A full-length CBS cDNA has been cloned. It is over 2500 bp long and encodes a polypeptide of 551 amino acids. Using this cDNA, 92 mutations in the CBS gene have been demonstrated in more than 300 alleles from individuals with CBS deficiency. Recently, the entire human CBS gene has been cloned and sequenced. It spans approximately 28 kbp, including 5 kbp of 5′-flanking sequence, and contains 23 exons. The CBS polypeptide is encoded by exons 1 to 16. Two alternatively used promoters have been identified approximately 5 kbp upstream from the initiator codon.

  • Routine screening of newborns for hypermethioninemia has been used to identify individuals with CBS deficiency. Striking regional differences in the rates of detection are present. The CBS deficiency of most detected individuals has been unresponsive to pyridoxine treatment, and it is virtually certain that a significant portion of CBS-deficient individuals, especially those responsive to pyridoxine, are being missed by current screening programs.

  • Management of CBS-deficient patients emphasizes amelioration ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.