Identification of Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Three Patients Previously Diagnosed with Long-Chain Acyl-CoA Dehydrogenase Deficiency

Abstract

ABSTRACT. Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of fatty acid 8-oxidation. Its diagnosis has been made based on the reduced activity of palmitoyl-CoA dehydrogenation, i.e., in fibroblasts. We previously showed that in immunoblot analysis, an LCAD band of normal size and intensity was detected in fibroblasts from all LCAD-deficient patients tested. In the present study, we amplified via polymerase chain reaction and sequenced LCAD cDNA from three of these LCADdeficient cell lines, and found perfectly normal LCAD sequences in two of them, indicating that at least these patients were not deficient in LCAD. The third patient was homozygous for an A to C substitution at 997, although it is unknown whether or not 997-C is a normal polymorphism. Although the LCAD sequence data were puzzling, a new enzyme, very-long-chain acyl-CoA dehydrogenase (VLCAD), was recently identified. Because VLCAD also has high activity ~vith palmitoyl-CoA as substrate, it was possible that defective VLCAD may cause reduced palmitoyl-CoA dehydrogenating activity. We performed immunoblot analysis of VLCAD in sis "LCAD-deficient" patients; VLCAD was negative in three of them, two of whom had a normal LCAD cDNA sequence. These results indicated that a considerable number of the patients who had previously been diagnosed as having LCAD deficiency in fact have VLCAD deficiency. (Pediatr Res 34: 11 1-1 13, 1993)

Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.

“…Microscopic examination of autopsy tissues revealed severe macrovesicular lipid storage in heart, liver, kidneys, and skeletal muscle. Patients 3, 4, and 5 were initially reported as having LCAD deficiency (12,13,25,26), but later, were shown to be deficient in VLCAD, rather than in LCAD, using immunoblot analysis (23). Patient 6 was reported previously to have LCAD deficiency (12,13), but has been found to be deficient in VLCAD in this study.…”

“…At the same time, skin fibroblasts from these two patients were found to have trace amounts of VLCAD protein in immunoblot analysis. Furthermore, three additional VLCAD patients were identified among those who were diagnosed previously as having LCAD deficiency (23).…”

Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse

“…), VLCAD (ACADVL [39]), and CPT-1A [40], but not CPT-1B or LCAD [41]. While homozygous CPT-1a deficiency is rare and potentially fatal in humans [40], heterozygous CPT-1a deficiency has not been reported with abnormalities.…”

Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: Identification of a novel mutation

“…VLCAD deficiency presents 2 phenotypes: a "severe" form characterized by an early onset of symptoms with hypertrophic cardiomyopathy and a high mortality rate and a "mild" form with hypoketot- ic hypoglycemia resembling mediumchain acyl-CoA dehydrogenase deficiency. [1][2][3][4][5][6] Adult onset has been reported with exercise-and fasting-induced muscle pain and rhabdomyolysis. 7,8 The reason for phenotypic variations in VLCAD deficiency is not well understood.…”