Familial carnitine transporter defect: A treatable cause of cardiomyopathy in children

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Abstract

Carnitine transporter defect is characterized by severely reduced transport of carnitine into skeletal muscle, fibroblasts, and renal tubules. All children with dilated cardiomyopathy or hypoglycemia and coma should be evaluated for this transporter defect because it is readily amenable to therapy that results in prolonged prevention of cardiac failure. This article details the cases of 3 children who have carnitine transporter defect, 2 of whom had severe dilated cardiomyopathy. Plasma and skeletal muscle carnitine levels were extremely low and both children were treated with oral L-carnitine, resulting in resolution of severe cardiomyopathy and prevention of recurrence or cardiac enlargement for more than 5 years. The third child had hypoglycemia and coma as presenting findings of the transporter defect and had mild left ventricular hypertrophy but no cardiac failure. The prognosis for long-term survival in pediatric dilated cardiomyopathy is poor. Children with carnitine transporter defect can have a different outcome if their underlying condition is detected early and treated medically. (Am Heart J 2000;139:S96-S106.)

Section snippets

Patient 1

A 6-and-a-half-year-old boy, who had a history of asthma, was admitted to the hospital for evaluation of cardiomegaly and congestive heart failure. Two years previously, a chest radiograph revealed that his heart size was at the upper limits of normal (Figure 1, A ).During the 6 weeks before admission, he had increasing fatigue and dyspnea. A chest radiograph showed severe cardiomegaly (Figure 1, B ). There was no family history of cardiac disease or sudden death, and the parents were not

Discussion

Long-chain fatty acids are an important energy substrate for the myocardium and other muscle tissue. Long-chain fatty acid metabolism depends on carnitine availability. Carnitine forms acylcarnitine esters with long-chain fatty acids and facilitates their transport across the inner mitochondrial membrane (Figure 9).Once inside the mitochondria, the long-chain fatty acids can undergo β-oxidation, thereby providing a critical source of energy for cardiac and skeletal muscle.[3], [11]

Carnitine

Conclusions

The low survival rate of children with dilated cardiomyopathy suggests that pediatricians and pediatric cardiologists need to take active measures to identify underlying causes so that appropriate treatment can be instituted. In the case of patients 1 and 2, the identification of their severe plasma and muscle carnitine deficiency was essential to the selection of L-carnitine therapy. For patient 1, the L-carnitine therapy was lifesaving and produced dramatic resolution of his severe congestive

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  • Cited by (0)

    Supported in part by the Ray and Hattie Anderson Center for the Study of Hereditary Cardiac Disease (Dr Pierpont), the Variety Club Association Gunshoots Program (Dr Pierpont), and the National Institutes of Health R01-DK-43841 and M01- RR00240 (Dr Stanley).

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