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.
Design: Examination of patterns of organic acids excreted in the urine before and following loading doses of isoleucine and methionine.
Setting: General clinical research center.
Patient: An infant with ethylmalonic aciduria, global developmental delay, acrocyanosis, and intermittent showers of petechiae.
Main outcome measure: 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.
Conclusion: In ethylmalonic acid encephalopathy with petechiae, methionine is a precursor of ethylmalonic acid.