title: The role of methionine in ethylmalonic encephalopathy with petechiae.
abstract: BACKGROUND
  Among patients with ethylmalonic aciduria, a subgroup with encephalopathy, petechial skin lesions, and often death in infancy is distinct from those with short-chain acyl-coenzyme A dehydrogenase deficiency or multiple acyl-coenzyme A dehydrogenase deficiency. The nature of the molecular defect in this subgroup is unknown, and the source of the ethylmalonic acid has been unclear.
  
  
  OBJECTIVE
  To determine whether the administration of candidate amino acids increased the excretion of ethylmalonic acid.
  
  
  METHODS
  Examination of patterns of organic acids excreted in the urine before and following loading doses of isoleucine and methionine.
  
  
  METHODS
  General clinical research center.
  
  
  METHODS
  An infant with ethylmalonic aciduria, global developmental delay, acrocyanosis, and intermittent showers of petechiae.
  
  
  METHODS
  Excretion of ethylmalonic acid in the urine.
  
  
  RESULTS
  Loading with methionine increased the excretion of ethylmalonic acid, whereas loading with isoleucine did not. Restriction of the dietary intake of methionine decreased ethylmalonic acid excretion.
  
  
  CONCLUSIONS
  In ethylmalonic acid encephalopathy with petechiae, methionine is a precursor of ethylmalonic acid.
authors.affiliation: Institute of Molecular Genetics and the Department of Pediatrics, University of California San Diego, La Jolla 92093, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: McGowan
authors.forename: William L
authors.initials: WL
authors.lastname: Nyhan
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Barshop
authors.forename: Robert K
authors.initials: RK
authors.lastname: Naviaux
authors.forename: Alice
authors.initials: A
authors.lastname: Yu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Haas
authors.forename: Jeannette J
authors.initials: JJ
authors.lastname: Townsend
mesh_terms: D000596:Amino Acids / Q000097:blood; D001921:Brain / Q000473:pathology; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D002421:Caudate Nucleus / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007532:Isoleucine / Q000008:administration & dosage / Q000502:physiology; D008297:Male; D008314:Malonates / Q000652:urine*; D008715:Methionine / Q000008:administration & dosage / Q000502:physiology*; D010375:Pedigree; D011693:Purpura / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D013378:Substantia Nigra / Q000473:pathology; D013577:Syndrome
chemical_list: D000596:Amino Acids; D008314:Malonates; D007532:Isoleucine; C038080:ethylmalonic acid; D008715:Methionine