TY - JOUR
T1 - A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts
AU - Burlina, Alberto B.
AU - Dionisi-Vici, Carlo
AU - Bennett, Michael J.
AU - Gibson, Kenneth M.
AU - Servidei, Serenella
AU - Bertini, Enrico
AU - Hale, Daniel
AU - Schmidt-Sommerfeld, Eberhard
AU - Sabetta, Gaetano
AU - Zacchello, Franco
AU - Rinaldo, Piero
N1 - Funding Information:
Supported in part by a Joseph Drown Foundation Award and by a Basil O'Connor Starter Scholar Research Award (5-91-0608) from the March of Dimes Birth Defect Foundation.
PY - 1994
Y1 - 1994
N2 - 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)
AB - 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)
UR - http://www.scopus.com/inward/record.url?scp=0028078632&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028078632&partnerID=8YFLogxK
U2 - 10.1016/S0022-3476(94)70257-8
DO - 10.1016/S0022-3476(94)70257-8
M3 - Article
C2 - 8283379
AN - SCOPUS:0028078632
SN - 0022-3476
VL - 124
SP - 79
EP - 86
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 1
ER -
