Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness

P. M. Coates, D. E. Hale, G. Finocchiaro, K. Tanaka, S. C. Winter

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Abstract

Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55% vs. controls of < 10%). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. controls of 14 ± 2 nmol/mg protein) and was 75% esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50% of control levels of acyl-CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 μM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50% of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect.

Original languageEnglish (US)
Pages (from-to)171-175
Number of pages5
JournalJournal of Clinical Investigation
Volume81
Issue number1
DOIs
StatePublished - Jan 1 1988

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Acyl-CoA Dehydrogenase
Carnitine
Muscle Weakness
Skeletal Muscle
Fibroblasts
Muscles
Electron-Transferring Flavoproteins
Slow-Twitch Muscle Fibers
Failure to Thrive
Antibodies
Vomiting
Proteins
Parents
Lipids
Enzymes
butyryl-coenzyme A
Short chain Acyl CoA dehydrogenase deficiency

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness",
abstract = "Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55{\%} vs. controls of < 10{\%}). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. controls of 14 ± 2 nmol/mg protein) and was 75{\%} esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50{\%} of control levels of acyl-CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 μM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50{\%} of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect.",
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Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness. / Coates, P. M.; Hale, D. E.; Finocchiaro, G.; Tanaka, K.; Winter, S. C.

In: Journal of Clinical Investigation, Vol. 81, No. 1, 01.01.1988, p. 171-175.

Research output: Contribution to journalArticle

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T1 - Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness

AU - Coates, P. M.

AU - Hale, D. E.

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AU - Tanaka, K.

AU - Winter, S. C.

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AB - Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55% vs. controls of < 10%). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. controls of 14 ± 2 nmol/mg protein) and was 75% esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50% of control levels of acyl-CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 μM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50% of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect.

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