Article

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

Unité 188 INSERM, Saint Vincent de Paul Hospital, Paris, France.
Pediatric Research (Impact Factor: 2.84). 11/1990; 28(6):657-662. DOI: 10.1203/00006450-199012000-00023

ABSTRACT A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood β-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's urine contained excessive amounts of the C6 to C10 dicarboxylic acids present in almost all defects of fatty acid mitochondrial oxidation. More specifically, gas chromatography-mass spectrometry identified an accumulation of medium- and long-chain (C8 to C14) 3-hydroxy-dicarboxylic acids, suggesting a defect of the mitochondrial enzyme that normally dehydrogenates these 3-hydroxyacyl-CoA esters. Biochemical studies in the patient's cultured fibroblasts confirmed the impairment of medium- and long-chain fatty acid oxidation, and allowed the recognition of the deficiency of long-chain 3-hydroxyacyl- CoA dehydrogenase. The activities of long-, medium-, and short-chain acyl-CoA dehydrogenases and 3-ketoacyl- CoA thiolase were normal. These results describe a disorder of fatty acid metabolism that affects the liver, skeletal muscles, and myocardium. It is important to point out that long-chain 3-hydroxyacyl-CoA deficiency shares many clinical similarities with systemic carnitine deficiency, as well as with carnitine-palmityl-CoA transferase and longchain acyl-CoA dehydrogenase deficiencies. The differential diagnosis of this disease relies on the demonstration of long-chain urinary dicarboxylic acids with a hydroxyl group in 3-position and the study of the enzyme activity in cultured fibroblasts.

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