Peroxisomal bifunctional enzyme deficiency

Paul A Watkins, W. W. Chen, C. J. Harris, G. Hoefler, S. Hoefler, D. C. Blake, A. Balfe, R. I. Kelley, Ann B. Moser, M. E. Beard, H. W. Moser

Research output: Contribution to journalArticle

Abstract

Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblast peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.

Original languageEnglish (US)
Pages (from-to)771-777
Number of pages7
JournalJournal of Clinical Investigation
Volume83
Issue number3
StatePublished - 1989

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Peroxisomal Disorders
Fibroblasts
Acetyl-CoA C-Acyltransferase
Acyl-CoA Oxidase
Peroxisomes
Enzymes
Enoyl-CoA Hydratase
Fatty Acids
3-Hydroxyacyl-CoA Dehydrogenase
Phytanic Acid
Plasmalogens
Density Gradient Centrifugation
Bile Acids and Salts
Catalase
Gonadal dysgenesis XX type deafness
Electron Microscopy
Phenotype
Messenger RNA
Acids
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Watkins, P. A., Chen, W. W., Harris, C. J., Hoefler, G., Hoefler, S., Blake, D. C., ... Moser, H. W. (1989). Peroxisomal bifunctional enzyme deficiency. Journal of Clinical Investigation, 83(3), 771-777.

Peroxisomal bifunctional enzyme deficiency. / Watkins, Paul A; Chen, W. W.; Harris, C. J.; Hoefler, G.; Hoefler, S.; Blake, D. C.; Balfe, A.; Kelley, R. I.; Moser, Ann B.; Beard, M. E.; Moser, H. W.

In: Journal of Clinical Investigation, Vol. 83, No. 3, 1989, p. 771-777.

Research output: Contribution to journalArticle

Watkins, PA, Chen, WW, Harris, CJ, Hoefler, G, Hoefler, S, Blake, DC, Balfe, A, Kelley, RI, Moser, AB, Beard, ME & Moser, HW 1989, 'Peroxisomal bifunctional enzyme deficiency', Journal of Clinical Investigation, vol. 83, no. 3, pp. 771-777.
Watkins PA, Chen WW, Harris CJ, Hoefler G, Hoefler S, Blake DC et al. Peroxisomal bifunctional enzyme deficiency. Journal of Clinical Investigation. 1989;83(3):771-777.
Watkins, Paul A ; Chen, W. W. ; Harris, C. J. ; Hoefler, G. ; Hoefler, S. ; Blake, D. C. ; Balfe, A. ; Kelley, R. I. ; Moser, Ann B. ; Beard, M. E. ; Moser, H. W. / Peroxisomal bifunctional enzyme deficiency. In: Journal of Clinical Investigation. 1989 ; Vol. 83, No. 3. pp. 771-777.
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AU - Harris, C. J.

AU - Hoefler, G.

AU - Hoefler, S.

AU - Blake, D. C.

AU - Balfe, A.

AU - Kelley, R. I.

AU - Moser, Ann B.

AU - Beard, M. E.

AU - Moser, H. W.

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