Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient with cystathionine β-synthase (CBS) deficiency
Article first published online: 4 JAN 2002
Copyright © 2002 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 108, Issue 1, pages 57–63, 15 February 2002
How to Cite
Yaghmai, R., Kashani, A. H., Geraghty, M. T., Okoh, J., Pomper, M., Tangerman, A., Wagner, C., Stabler, S. P., Allen, R. H., Mudd, S. H. and Braverman, N. (2002), Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient with cystathionine β-synthase (CBS) deficiency. Am. J. Med. Genet., 108: 57–63. doi: 10.1002/ajmg.10186
- Issue published online: 16 JAN 2002
- Article first published online: 4 JAN 2002
- Manuscript Accepted: 11 OCT 2001
- Manuscript Received: 28 FEB 2001
- cerebral edema
Cystathionine β-synthase (CBS) deficiency, the most common form of homocystinuria, is an autosomal recessive inborn error of homocysteine metabolism. Treatment of B6-nonresponsive patients centers on lowering homocysteine and its disulfide derivatives (tHcy) by adherence to a methionine-restricted diet. However, lifelong dietary control is difficult. Betaine supplementation is used extensively in CBS-deficient patients to lower plasma tHcy. With betaine therapy, methionine levels increase over baseline, but usually remain below 1,500 μmol/L, and these levels have not been associated with adverse affects. We report a child with B6-nonresponsive CBS deficiency and dietary noncompliance whose methionine levels reached 3,000 μmol/L on betaine, and who subsequently developed massive cerebral edema without evidence of thrombosis. We investigated the etiology by determining methionine and betaine metabolites in our patient, and several possible mechanisms for her unusual response to betaine are discussed. We conclude that the cerebral edema was most likely precipitated by the betaine therapy, although the exact mechanism is uncertain. This case cautions physicians to monitor methionine levels in CBS-deficient patients on betaine and to consider betaine as an adjunct, not an alternative, to dietary control. © 2002 Wiley-Liss, Inc.