Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency

clinical and biochemical differences with the fatal cardiac phenotype

H R Scholte, R N Van Coster, P C de Jonge, B J Poorthuis, J A Jeneson, B S Andresen, N Gregersen, J B de Klerk, H F Busch

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. Fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. Fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38% of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio.

OriginalsprogEngelsk
TidsskriftNeuromuscular Disorders
Vol/bind9
Udgave nummer5
Sider (fra-til)313-9
Antal sider7
ISSN0960-8966
StatusUdgivet - jul. 1999

Fingeraftryk

Muscular Diseases
Fibroblasts
Oleic Acid
Palmitoylcarnitine
Myoglobinuria
Muscles
Phosphocreatine
Palmitates
Myalgia
Oxidative Phosphorylation
Muscle Weakness
Myristic Acid
Base Pairing
Lysine
Fasting
Exercise
Lipids
Enzymes

Citer dette

Scholte, H. R., Van Coster, R. N., de Jonge, P. C., Poorthuis, B. J., Jeneson, J. A., Andresen, B. S., ... Busch, H. F. (1999). Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency: clinical and biochemical differences with the fatal cardiac phenotype. Neuromuscular Disorders, 9(5), 313-9.
Scholte, H R ; Van Coster, R N ; de Jonge, P C ; Poorthuis, B J ; Jeneson, J A ; Andresen, B S ; Gregersen, N ; de Klerk, J B ; Busch, H F. / Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency : clinical and biochemical differences with the fatal cardiac phenotype. I: Neuromuscular Disorders. 1999 ; Bind 9, Nr. 5. s. 313-9.
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abstract = "A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. Fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. Fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38{\%} of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio.",
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author = "Scholte, {H R} and {Van Coster}, {R N} and {de Jonge}, {P C} and Poorthuis, {B J} and Jeneson, {J A} and Andresen, {B S} and N Gregersen and {de Klerk}, {J B} and Busch, {H F}",
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Scholte, HR, Van Coster, RN, de Jonge, PC, Poorthuis, BJ, Jeneson, JA, Andresen, BS, Gregersen, N, de Klerk, JB & Busch, HF 1999, 'Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency: clinical and biochemical differences with the fatal cardiac phenotype', Neuromuscular Disorders, bind 9, nr. 5, s. 313-9.

Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency : clinical and biochemical differences with the fatal cardiac phenotype. / Scholte, H R; Van Coster, R N; de Jonge, P C; Poorthuis, B J; Jeneson, J A; Andresen, B S; Gregersen, N; de Klerk, J B; Busch, H F.

I: Neuromuscular Disorders, Bind 9, Nr. 5, 07.1999, s. 313-9.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Myopathy in very-long-chain acyl-CoA dehydrogenase deficiency

T2 - clinical and biochemical differences with the fatal cardiac phenotype

AU - Scholte, H R

AU - Van Coster, R N

AU - de Jonge, P C

AU - Poorthuis, B J

AU - Jeneson, J A

AU - Andresen, B S

AU - Gregersen, N

AU - de Klerk, J B

AU - Busch, H F

PY - 1999/7

Y1 - 1999/7

N2 - A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. Fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. Fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38% of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio.

AB - A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. Fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. Fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38% of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio.

KW - Acyl-CoA Dehydrogenase, Long-Chain

KW - Acyl-CoA Dehydrogenases

KW - Adolescent

KW - Adult

KW - Cardiomyopathy, Hypertrophic

KW - Carnitine

KW - DNA Mutational Analysis

KW - Diagnosis, Differential

KW - Fatal Outcome

KW - Fibroblasts

KW - Humans

KW - Magnetic Resonance Spectroscopy

KW - Male

KW - Mitochondria, Muscle

KW - Muscle, Skeletal

KW - Muscular Diseases

KW - Mutation

KW - Phenotype

KW - Sequence Deletion

M3 - Journal article

VL - 9

SP - 313

EP - 319

JO - Neuromuscular Disorders

JF - Neuromuscular Disorders

SN - 0960-8966

IS - 5

ER -