Carnitine uptake defect

Lamhonwah AM, Tein I. Carnitine uptake defect frameshift mutations in the human plasmalemmal carnitine transporter gene. Biochem Biophys Res Commun 1998 252(2) 396-401. 

Carnitine uptake defect 2I2I40 Garnitine transporter <1 100,000 Hypoglycemia, cardiomyopathy ... 

Disorders of carnitine metabolism Carnitine uptake defect... 

HHH) syndrome Dibasic aminoaciduria Carnitine uptake defect CPT 1... 

Carnitine uptake defect (CUD, 14.1) is due to a defect in the high-affinity carnitine transporter [1]. Plasma free and total carnitine levels are extremely low. Clinically two forms exist an early childhood-onset cardiomyopathic form and a hepatic form with recurrent crises of Reye-like syndrome. In general the response to oral carnitine supplements is very good. Plasma acylcarnitines are normal, there are scattered reports on moderate dicarboxylic aciduria. 

Signs and Symptoms Table 14.1. Carnitine uptake defect (23 patients) ... 

Generalized carnitine deficiency, in its primary form and inherited as an autosomal recessive trait, is due to a defect of the specific high-affinity, low-concentration, carrier-mediated carnitine-uptake mechanism. The defect has been documented in cultured fibroblasts and muscle cultures, but the same uptake system is probably shared by heart and kidney, thus explaining the cardiomyopathy and the excessive leakage of carnitine into the urine. Oral L-carnitine supplementation results in dramatic improvement in cardiac function [4,8]. 

Al Odaib and colleagues have described two children who had recurrent episodes of liver disease culminating in liver failure and who underwent liver transplantation [18]. The laboratory data, as well as the hepatic acyl-carnitine profile in one of those patients, were interpreted as suggestive of a fatty acid oxidation disorder. Cultured fibroblasts derived from both patients showed a moderate reduction in the uptake and oxidation of oleic and palmitic acid. It was concluded that an impairment in the uptake of long-chain fatty acids, probably caused by a defective transporter, was the cause of liver disease in these patients [18]. The molecular defect remains undetermined in particular, the relationship between this putative Tiver/fi-broblast LCFA transporter and the widely expressed CD36/LCFA transporter molecule, a genetic deficiency of which is rather common and may be implicated in cardiomyopathy, is unclear [19]. 

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