Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency

Indo, Yasuhiro; Coates, Paul M.; Hale, Daniel E.; Tanaka, Kay

doi:10.1203/00006450-199109000-00001

Cited by 20 publications

(11 citation statements)

References 18 publications

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“…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.…”

Section: Case Historycontrasting

confidence: 37%

“…The case histories were partially described in the previous reports (12,13,22,(24)(25)(26). We describe them as follows.…”

Section: Case Historymentioning

confidence: 99%

“…In contrast to MCAD deficiency, other defects, such as short-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase (LCAD) deficiencies, are rare. The detailed clinical descriptions of these defects are quite variable, and many patients die before 1 yr of age (12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

“…Within the group of acyl-coenzyme A (CoA) dehydrogenases that catalyze the first reaction in the mitochondrial /3-oxidation of straight-chain fatty acid of various chain lengths, deficiencies of three enzymes have been reported (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Among these defects, medium-chain acyl-CoA dehydrogenase (MCAD)' deficiency is relatively common.…”

Section: Introductionmentioning

confidence: 99%

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

Aoyama¹,

Souri²,

Ushikubo³

et al. 1995

J. Clin. Invest.

171

131

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Mitochondrial very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) was purified from human liver. The molecular masses of the native enzyme and the subunit were estimated to be 154 and 70 kD, respectively. The enzyme was found to catalyze the major part of mitochondrial palmitoylcoenzyme A dehydrogenation in liver, heart, skeletal muscle, and skin fibroblasts (89-97, 86-99, 96-99, and 78-87%, respectively).Skin fibroblasts from 26 patients suspected of having a disorder of mitochondrial a-oxidation were analyzed for VLCAD protein using immunoblotting, and 7 of them contained undetectable or trace levels of the enzyme. The seven deficient fibroblast lines were characterized by measuring acyl-coenzyme A dehydrogenation activities, overall palmitic acid oxidation, and VLCAD protein synthesis using pulse-chase, further confirming the diagnosis of VLCAD deficiency. These results suggested the heterogenous nature of the mutations causing the deficiency in the seven patients.Clinically, all patients with VLCAD deficiency exhibited cardiac disease. At least four of them presented with hypertrophic cardiomyopathy. This frequency (> 57%) was much higher than that observed in patients with other disorders of mitochondrial long-chain fatty acid oxidation that may be accompanied by cardiac disease in infants. (J. Clin. Invest. 1995Invest. . 95:2465Invest. -2473

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Section: Case Historycontrasting

confidence: 37%

“…The case histories were partially described in the previous reports (12,13,22,(24)(25)(26). We describe them as follows.…”

Section: Case Historymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Aoyama¹,

Souri²,

Ushikubo³

et al. 1995

J. Clin. Invest.

171

131

View full text Add to dashboard Cite

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“…Thus, the diagnosis of LCAD deficiency has been made based on the reduced dehydrogenase activity toward palmitoyl-CoA in the soluble cell fraction of cells such as fibroblasts or leukocytes (9). Recently, we reported that, among nine LCAD-deficient cell lines, all exhibited a positive protein band that was immunoreactive with anti-LCAD antibody, had a normal molecular mass and normal intensity (10). This result appeared to suggest that all cases of LCAD deficiency were caused by a point mutation in the LCAD gene.…”

mentioning

confidence: 76%

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

et al. 1993

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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)

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New developments in the diagnosis and investigation of mitochondrial fatty acid oxidation disorders

Coates

1994

Eur J Pediatr

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Since the discovery of muscle carnitine palmitoyltransferase deficiency in 1973, a dozen separate defects of mitochondrial fatty acid beta-oxidation in man have been identified. With the exception of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, which occurs with a frequency approaching 1:10,000 among Caucasians of Northern European origin, the other defects are quite rare. Collectively, however, they are common causes of disease resembling Reye syndrome in early life, and some have a later and more chronic presentation with cardiomyopathy and skeletal muscle weakness. They also represent a small, but significant, proportion of cases of sudden and unexplained death within the first 2 years of life. Diagnosis of these disorders has become increasingly sophisticated, with the advent of new analytical technologies and an increased awareness of the appropriate clinical and laboratory investigations needed in order to evaluate potential defects of this pathway. The combination of provocative testing (e.g., carnitine loading, phenylpropionic acid loading, long-chain fat loading) and advanced analytical techniques for the measurement of blood and urinary metabolites (e.g., tandem fast atom bombardment-mass spectrometry, stable isotope dilution gas chromatography-mass spectrometry) permits a specific diagnosis in the case of several, although not all, of the disorders of this pathway. Methods for the measurement of all of the enzymes of beta-oxidation are now available to enhance this diagnostic capability. There remain, however, many patients in whom clinical and laboratory signs point to a defect in beta-oxidation, but in whom no specific diagnosis has yet been made.(ABSTRACT TRUNCATED AT 250 WORDS)

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Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency

Cited by 20 publications

References 18 publications

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

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

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

New developments in the diagnosis and investigation of mitochondrial fatty acid oxidation disorders

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