Carnitine deficiency presenting as familial cardiomyopathy: A treatable defect in carnitine transport

Waber, Lewis; Valle, David; Neill, Catherine A.; DiMauro, Salvatore; Shug, Austin L.

doi:10.1016/s0022-3476(82)80294-1

Cited by 228 publications

(71 citation statements)

References 11 publications

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“…In conclusion, it is important to point out the clinical and biochemical similarities between our observation and other defects in fatty acid oxidation, such as LCAD deficiency (2,6), systemic carnitine deficiency (25), and carnitine-palmityltransferase deficiency (26). The muscular and cardiac involvement observed in our patient is consistent with the hypothesis that the accumulation of long-chain dicarboxylic acids, which occurs in all of these disorders, is directly toxic to these tissues (6).…”

Section: Discussionsupporting

confidence: 85%

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

et al. 1990

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ABSTRACT. A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood P-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's urine contained excessive amounts of the Cs to Clo dicarboxylic acids present in almost all defects of fatty acid mitochondrial oxidation. More specifically, gas chromatography-mass spectrometry identified an accumulation of medium-and long-chain (Cs to C14) 3-hydroxy-dicarboxylic acids, suggesting a defect of the mitochondrial enzyme that normally dehydrogenates these 3-hydroxyacyl-CoA esters. Biochemical studies in the patient's cultured fibroblasts confirmed the impairment of medium-and long-chain fatty acid oxidation, and allowed the recognition of the deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase. The activities of long-, medium-, and short-chain acyl-CoA dehydrogenases and 3-ketoacylCoA thiolase were normal. These results describe a disorder of fatty acid metabolism that affects the liver, skeletal muscles, and myocardium. It is important to point out that long-chain 3-hydroxyacyl-CoA deficiency shares many clinical similarities with systemic carnitine deficiency, as well as with carnitine-palmityl-CoA transferase and longchain acyl-CoA dehydrogenase deficiencies. The differential diagnosis of this disease relies on the demonstration of long-chain urinary dicarboxylic acids with a hydroxyl group in 3-position and the study of the enzyme activity in cultured fibroblasts. (Pediatr Res 28: 657-662, 1990)

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Section: Discussionsupporting

confidence: 85%

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

et al. 1990

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“…Rarely, a metabolic etiology responsive to specific therapy is identified. For example, previous reports have described reversal of the hemodynamic and morphologic abnormalities of cardiomyopathy with treatment of pheochromocytoma (1), hypocalcemia (2,3), and carnitine deficiency (4,5). The "myxedema heart" was first described by Zondek (6), who noted a dilated cardiac silhouette, slow indolent heart action, and low electrocardiographic voltage, which were all corrected by thyroid hormone therapy.…”

mentioning

confidence: 99%

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Ladenson

Sherman

Baughman

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

158

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Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysmuction in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid young man with dilated cardiomyopathy. Before and during 9 months of thyroxine therapy, serial assessment ofmyocardial performance documented substantial improvements in the left ventricular ejection fraction (16-37%), left ventricular end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters'min-1-m-2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured in biopsy samples obtained before and after thyroxine replacement. In comparison with myocardium from nonfailing control hearts, this patient's pretreatment a-myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic factor mRNA level was markedly elevated, and the phospholamban mRNA level was decreased. All of these derangements were reversed 9 months after restoration of euthyroidism. These observations in an unusual patient with profound myxedema and cardiac dilatation permit correlation between the reversible changes in myocardial function and steady-state mRNA levels in a cardiomyopathy. They suggest that alterations in gene expression in the dilated myopathic heart may be correctable when a treatable cause is identified.Most patients with dilated cardiomyopathy have a poor long-term prognosis, with progressive myocardial dysfunction. Rarely, a metabolic etiology responsive to specific therapy is identified. For example, previous reports have described reversal of the hemodynamic and morphologic abnormalities of cardiomyopathy with treatment of pheochromocytoma (1), hypocalcemia (2, 3), and carnitine deficiency (4, 5). The "myxedema heart" was first described by Zondek (6), who noted a dilated cardiac silhouette, slow indolent heart action, and low electrocardiographic voltage, which were all corrected by thyroid hormone therapy. Although invasive (7) and noninvasive (8) studies have since confirmed that thyroid hormone deficiency is associated with a reversible decrease in myocardial contractility, it has remained controversial whether hypothyroidism alone can cause a dilated cardiomyopathy and clinical heart failure. Furthermore, although effects of thyroid hormones on myocardial myosin isoenzyme expression (9, 10), 3-adrenergic receptor number (11), sarcoplasmic reticulum calcium exchange (12), and guanine nucleotide-binding regulatory proteins (13) have all been described in experimental animals, the fundamental pathogenesis of myocardial dysfunction caused by thyroid hormone deficiency in humans has remained uncertain.We report a young man with a dilated cardiomyopathy and profound hypothyroidism. During 9 months of thyroid hormone replacement therapy, serial clinical observations and noninvasive cardiovascular function tests documented substantial improvement in myocardial performance. Quantitation of steady-state mRNA levels in endomyocardial biops...

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“…Unexpectedly, there have been only a few reports that give the detail informations about the cardiomyopathy. In clinical and pathological analysis, congestive heart failure, accumulations of triglycerides and increases of mitochondria have been only described [8,9].…”

Section: Introductionmentioning

confidence: 99%

Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency

et al. 1993

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We have reported the clinical and biochemical findings in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency. This paper is the first report about cardiomyopathy injvs mice. Adult jvs mice (at the age of 2 3 months) show cardiac hypertrophy which is caused by enlargement of the cardiac muscle cell associated with increases of non-collagen protein and DNA content. Carnitine administration (2 mg/head, twice a day, from 1 month of age) significantly suppresses the cardiac hypertrophy, showing that carnitine deficiency plays an important role in the development of the cardiac hypertrophy. The discovery of cardiac hypertrophy in carnitine-deficient jvs mice will lead to clarification of the pathophysiology of cardiomyopathy in systemic carnitine deficiency in human beings.Cardiac hypertrophy; Systemic carnitine deficiency; Animal model; Juvenile visceral steatosis mice

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Carnitine deficiency presenting as familial cardiomyopathy: A treatable defect in carnitine transport

Cited by 228 publications

References 11 publications

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism.

Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency

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