title: Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient with cystathionine beta-synthase (CBS) deficiency.
abstract: Cystathionine beta-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 micromol/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 micromol/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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Yaghmai
authors.forename: Amir H
authors.initials: AH
authors.lastname: Kashani
authors.forename: Michael T
authors.initials: MT
authors.lastname: Geraghty
authors.forename: Jay
authors.initials: J
authors.lastname: Okoh
authors.forename: Martin
authors.initials: M
authors.lastname: Pomper
authors.forename: Albert
authors.initials: A
authors.lastname: Tangerman
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Sally P
authors.initials: SP
authors.lastname: Stabler
authors.forename: Robert H
authors.initials: RH
authors.lastname: Allen
authors.forename: S Harvey
authors.initials: SH
authors.lastname: Mudd
authors.forename: Nancy
authors.initials: N
authors.lastname: Braverman
mesh_terms: D001622:Betaine / Q000009:adverse effects* / Q000378:metabolism; D001929:Brain Edema / Q000097:blood / Q000139:chemically induced / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006712:Homocystinuria / Q000150:complications* / Q000178:diet therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008715:Methionine / Q000097:blood*; D016312:Treatment Refusal
chemical_list: D001622:Betaine; D008715:Methionine