A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts

Alberto B. Burlina, Carlo Dionisi-Vici, Michael J. Bennett, Kenneth M. Gibson, Serenella Servidei, Enrico Bertini, Daniel Hale, Eberhard Schmidt-Sommerfeld, Gaetano Sabetta, Franco Zacchello, Piero Rinaldo

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


We describe four Italian male infants with a novel clinical phenotype characterized by orthostatic acrocyanosis, relapsing petechiae, chronic diarrhea, progressive pyramidal signs, mental retardation, and brain magnetic resonance imaging abnormalities. The first symptoms appeared after the termination of breast-feeding and introduction of formula feeding. Marked persistent 2-ethylmalonic aciduria was associated with abnormal excretion of C4-C5(n-butyryl-, isobutyryl-, isovaleryl-, and 2-methylbutyryl-) acylglycines and acylcarnitines and with intermittent lactic acidosis. Short- and branched-chain plasma acylcarnitine levels were also elevated. 2-Ethylmalonic aciduria is generally regarded as being indicative of a defect in fatty acid oxidation. Extensive studies of cultured fibroblasts failed to reveal such a defect. The observation of intermittent urinary excretion of 2-ethylhydracrylic acid pointed to involvement of the isoleucine R pathway in ethylmalonate biosynthesis. This hypothesis was tentatively corroborated by the biochemical responses to an oral isoleucine challenge in two patients. However, fibroblast studies showed normal oxidation rates of [14C]isoleucine (ul), indicating that this is not a defect of isoleucine oxidation expressed in skin fibroblasts. In one of two patients tested, cytochrome c oxidase activity was partially reduced (45%) in cultured fibroblasts. This unique clinical and biochemical phenotype identifies a new metabolic encephalopathy of yet undetermined cause. (J PEDIATR 1994;124:79-86)

Original languageEnglish (US)
Pages (from-to)79-86
Number of pages8
JournalJournal of Pediatrics
Issue number1
StatePublished - 1994

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health


Dive into the research topics of 'A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts'. Together they form a unique fingerprint.

Cite this