THE CLINICAL SPECTRUM OF LONG-CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE-DEFICIENCY

Four patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase d eficiency are presented, Clinical onset in the form of acute encephalo pathy occurred between the ages of 9 months and 3 years, The clinical course included recurrent metabolic crises in 4 patients, cardiac invo lvement and retinopathy in 3, and myopathy in 2. None had signs of per ipheral neuropathy, Three patients died and one is currently well, Hyp oketotic hypoglycemia with C6-C14 3-hydroxy-dicarboxylic aciduria duri ng metabolic crises associated with decreased plasma carnitine levels was the main biochemical finding, Enzymologic studies disclosed long-c hain 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 biopsie s disclosed nonspecific degenerative changes in 2 patients and were no rmal in the remaining 2, Ultrastructural abnormalities in mitochondria were found in 3 patients. A review of the literature combined with th e data from our series (total 22 patients) disclosed acute clinical on set in 77% of cases and subacute in 23%. In the combined series, the a verage age at onset was 11 months, family history was positive in 32% of patients and overall mortality was 50%, We describe the clinical sp ectrum of this disease and emphasize that, among patients with suspect ed beta-oxidation defects the finding of pigmentary retinopathy should lead to the suspicion of long-chain 3-hydroxyacyl-coenzyme A-dehydrog enase deficiency.