Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient with cystathionine β-synthase (CBS) deficiency

Reza Yaghmai, Amir H. Kashani, Michael T. Geraghty, Jay Okoh, Martin Pomper, Albert Tangerman, Conrad Wagner, Sally P. Stabler, Robert H. Allen, S. Harvey Mudd, Nancy Braverman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalAmerican journal of medical genetics
Volume108
Issue number1
DOIs
StatePublished - Feb 15 2002

Keywords

  • Betaine
  • Cerebral edema
  • Homocystinuria
  • Methionine

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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