title: Infantile hypermethioninemia and hyperhomocysteinemia due to high methionine intake: a diagnostic trap.
abstract: Studies were carried out to identify the cause of combined severe hypermethioninemia and moderate hyperhomocysteinemia in a cluster of 10 infants ascertained between 1999 and early 2001. Although several were thought initially to have cystathionine beta-synthase (CBS) deficiency and treated accordingly, CBS deficiency and other known genetic causes of hypermethioninemia were ruled out by assay of CBS activity in fibroblasts of four patients and by assays of plasma cystathionine and S-adenosylmethionine. Retrospective data on dietary methionine intakes and plasma concentrations of methionine and related metabolites established that the hypermethioninemia in nine of the 10 babies was related to ingestion of an infant protein hydrolysate formula, the methionine content of which had been increased from May 1998 to February 2001. The formula in question has now been reformulated and is no longer available. The 10th infant manifested similar metabolic abnormalities while receiving TPN containing excessive methionine. Brain MRI abnormalities indicative of cerebral edema, most marked in the cerebral cortex and posterior brainstem, occurred in two patients near times of extreme hypermethioninemia. Metabolic and MRI abnormalities resolved when the methionine intake decreased. A third infant had a normal MRI 1 day after the formula was changed. The possible relationship between extreme hypermethioninemia and cerebral edema is discussed and a working hypothesis offered to explain the relative sensitivity of the inferior colliculi, based upon the facts that this is the region most active in glucose utilization and that Na(+),K(+)-ATPase is inhibited by methionine and related metabolites.
authors.affiliation: NIMH/DIRP/LMB, Laboratory of Molecular Biology, National Institute of Mental Health, Building 36, Room 1B-08, 36 Convent Drive, MSC 4034, Bethesda, MD 20892-4034, USA. shm@codon.nih.gov
authors.forename: S
authors.initials: S
authors.lastname: Harvey Mudd
authors.forename: Nancy
authors.initials: N
authors.lastname: Braverman
authors.forename: Martin
authors.initials: M
authors.lastname: Pomper
authors.forename: Kamer
authors.initials: K
authors.lastname: Tezcan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kronick
authors.forename: Parul
authors.initials: P
authors.lastname: Jayakar
authors.forename: Cheryl
authors.initials: C
authors.lastname: Garganta
authors.forename: Mary G
authors.initials: MG
authors.lastname: Ampola
authors.forename: Harvey L
authors.initials: HL
authors.lastname: Levy
authors.forename: Shawn E
authors.initials: SE
authors.lastname: McCandless
authors.forename: Hobart
authors.initials: H
authors.lastname: Wiltse
authors.forename: Sally P
authors.initials: SP
authors.lastname: Stabler
authors.forename: Robert H
authors.initials: RH
authors.lastname: Allen
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Marlene W
authors.initials: MW
authors.lastname: Borschel
mesh_terms: D001929:Brain Edema / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005527:Food, Fortified / Q000009:adverse effects*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology*; D007223:Infant; D007225:Infant Food / Q000009:adverse effects*; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000097:blood*
chemical_list: D008715:Methionine