title: The clinical spectrum of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
abstract: Four patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are presented. Clinical onset in the form of acute encephalopathy occurred between the ages of 9 months and 3 years. The clinical course included recurrent metabolic crises in 4 patients, cardiac involvement and retinopathy in 3, and myopathy in 2. None had signs of peripheral neuropathy. Three patients died and one is currently well. Hypoketotic hypoglycemia with C6-C14 3-hydroxy-dicarboxylic aciduria during metabolic crises associated with decreased plasma carnitine levels was the main biochemical finding. Enzymologic studies disclosed long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency in all patients. Homozygosity for a G to C mutation at position 1528 in the encoding region of the enzyme was found in 2 patients. Histologic and electron microscopic studies of liver biopsy specimens revealed steatosis in 3 patients and mitochondrial abnormalities in 2. Skeletal muscle biopsies disclosed nonspecific degenerative changes in 2 patients and were normal in the remaining 2. Ultrastructural abnormalities in mitochondria were found in 3 patients. A review of the literature combined with the data from our series (total 22 patients) disclosed acute clinical onset in 77% of cases and subacute in 23%. In the combined series, the average age at onset was 11 months, family history was positive in 32% of patients and overall mortality was 50%. We describe the clinical spectrum of this disease and emphasize that, among patients with suspected beta-oxidation defects the finding of pigmentary retinopathy should lead to the suspicion of long-chain 3-hydroxyacyl-coenzyme A-dehydrogenase deficiency.
authors: Child Neurology Unit, Vall d'Hebron University Hospital, Barcelona, Spain.
authors: R
authors: R
authors: Pons
authors: M
authors: M
authors: Roig
authors: E
authors: E
authors: Riudor
authors: A
authors: A
authors: Ribes
authors: P
authors: P
authors: Briones
authors: L
authors: L
authors: Ortigosa
authors: A
authors: A
authors: Baldellou
authors: J
authors: J
authors: Gil-Gibernau
authors: M
authors: M
authors: Olesti
authors: C
authors: C
authors: Navarro
authors: R J
authors: RJ
authors: Wanders
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D001927:Brain Diseases / Q000209:etiology; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology; D008659:Metabolic Diseases / Q000209:etiology; D008928:Mitochondria / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases