The clinical spectrum of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

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.