The role of methionine in ethylmalonic encephalopathy with petechiae.
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.
McGowan
Karen A
KA
Institute of Molecular Genetics and the Department of Pediatrics, University of California San Diego, La Jolla 92093, USA.
Nyhan
William L
WL
Barshop
Bruce A
BA
Naviaux
Robert K
RK
Yu
Alice
A
Haas
Richard H
RH
Townsend
Jeannette J
JJ
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
D000596:Amino Acids; D008314:Malonates; D007532:Isoleucine; C038080:ethylmalonic acid; D008715:Methionine