ABSTRACT
A specific type of disorder in which ethylmalonic aciduria is associated with a very different phenotype and normal oxidation of fatty acids was first reported in 1991 and 1994. After the delineation of the molecular defect in the ETHE1 gene, this disease was distinguished as ethylmalonic encephalopathy. Ethylmalonic encephalopathy may masquerade as a hematologic disorder and the patient suffered from progressive pancytopenia, in addition to progressive psychomotor retardation. In one child with ethylmalonic encephalopathy due to a homozygous mutation in the ETHE1 gene (R163W), no pathologic excretion of ethylmalonic acid was found, and the clinical picture was suggestive of a connective tissue disorder (vascular fragility, joint hyperlaxity, delayed motor development, and normal cognitive development). Over 30 mutations in ETHE1 have been found in patients with ethylmalonic encephalopathy. The disease is generally lethal in infancy or early childhood. Treatment with riboflavin, carnitine, glycine, and vitamin E have been without evident effect.
