One-methyl group metabolism in non-ketotic hyperglycinaemia: mildly elevated cerebrospinal fluid homocysteine levels.

Journal Article (Journal Article)

Non-ketotic hyperglycinaemia (NKH) is a rare, severe brain disease caused by deficient glycine cleavage enzyme complex activity resulting in elevated glycine concentrations. Recent experience suggests that factors in addition to glycine kinetics are involved in its pathogenesis. The glycine cleavage reaction through the formation of methylenetetrahydrofolate is an important one-methyl group donor. A deficiency in one-methyl group metabolites, in particular of choline, has been hypothesized in NKH. We investigated metabolites involved in one-methyl group metabolism in plasma and CSF of 8 patients with NKH, and monitored the effect of treatment with choline in one patient. Plasma and CSF choline and phosphatidylcholine concentrations were normal, except for a low plasma choline in the single neonate studied. Choline treatment did not change brain choline content, and was not associated with clinical or radiological improvement. Methionine concentrations and, in one-patient, S-adenosylmethionine and 5-methyltetrahydrofolate concentrations were normal in CSF. Homocysteine concentrations in CSF, however, were slightly but consistently elevated in all four patients examined, but cysteine, cysteinylglycine and glutathione were normal. Serine is important in the transfer of one-methyl groups from mitochondria to cytosol. Serine concentrations were normal in plasma and CSF, but dropped to below normal in CSF in three patients on benzoate treatment. These observations add to our understanding of the complex metabolic disturbances in NKH.

Full Text

Duke Authors

Cited Authors

  • Van Hove, JL; Lazeyras, F; Zeisel, SH; Bottiglieri, T; Hyland, K; Charles, HC; Gray, L; Jaeken, J; Kahler, SG

Published Date

  • December 1998

Published In

Volume / Issue

  • 21 / 8

Start / End Page

  • 799 - 811

PubMed ID

  • 9870205

International Standard Serial Number (ISSN)

  • 0141-8955

Digital Object Identifier (DOI)

  • 10.1023/a:1005462400552


  • eng

Conference Location

  • United States