Deficient muscle carnitine transport in primary carnitine deficiency

Primary carnitine deficiency is associated with deficient blood and tissue carnitine concentrations. The clinical syndrome is dominated by heart and skeletal muscle symptoms, and the clinical response to oral carnitine supplementation is life-saving. Carnitine uptake has been shown to be defective in cultured skin fibroblasts and leukocytes obtained from patients with this condition. We report a new case of primary carnitine deficiency and offer direct evidence consistent with an impairment of carnitine uptake in differentiating muscle culture. The patient presented with severe and progressive cardiomyopathy and moderate proximal limb weakness. Plasma and muscle carnitine levels were very low, and the maximal rate of carnitine transport in cultured fibroblasts was deficient. An asymptomatic sister with intermediate levels of carnitine in plasma showed partially deficient carnitine uptake in fibroblasts, indicating heterozygosity. The patient's condition improved dramatically with oral carnitine therapy. Further studies were performed in cultured muscle cells at different stages of maturation, which demonstrated deficient maximal rates of carnitine uptake. Our findings are consistent with the concept that primary carnitine deficiency is the result of a generalized defect involving carnitine transport across tissue membranes.