LONG-CHAIN 3-HYDROXYACYL-COENZYME-A DEHYDROGENASE-DEFICIENCY WITH THEG1528C MUTATION - CLINICAL PRESENTATION OF 13 PATIENTS

Long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase is one of thre e enzyme activities of the mitochondrial trifunctional protein. We rep ort the clinical findings of 13 patients with long-chain 3-hydroxyacyl -CoA dehydrogenase deficiency. At presentation the patients had had hy poglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during the first 2 years of life. Seven patients had recurrent metabolic cris es, and six patients had a steadily progressive course. Two patients h ad cholestatic liver disease, which is uncommon in beta-oxidation defe cts. One patient had peripheral neuropathy, and six patients had retin opathy with focal pigmentary aggregations or retinal hypopigmentation. All patients were homozygous for the common mutation G1528C. However, the enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities of the mitochondrial trifunctional protein were variably decreased in skin f ibroblasts. Dicarboxylic aciduria was detected in 9 of 10 patients, an d most patients had lactic acidosis, increased serum creatine kinase a ctivities, and low serum carnitine concentration. Neuroradiologically there was bilateral periventricular or focal cortical lesions in three patients, and brain atrophy in one. Only one patient, who has had die tary treatment for 9 years, is alive at the age of 14 years; all other s died before they were 2 years of age. Recognition of the clinical fe atures of long-chain 3-hydroxyacyl-CoA deficiency is important for the early institution of dietary management, which may alter the otherwis e invariably poor prognosis.