Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency

Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal r ecessive disease characterized by low serum and intracellular concentration s of carnitine, CDSP may present with acute metabolic derangement simulatin g Reye's syndrome within the first 2 years of life. After 3 years of age, p atients with CDSP may present with cardiomyopathy and muscle weakness. A li nkage with D5S436 in 5q was reported in a family, A recently cloned homolog ue of the organic cation transporter, OCTN2, which has sodium-dependent car nitine uptake properties, was also mapped to the same locus. We screened fo r mutation in OCTN2 in a confirmed CDSP family. One truncating mutation (Tr p132Stop) and one missense mutation (Pro478Leu) of OCTN2 were identified to gether with two silent polymorphisms, Expression of the mutant cDNAs reveal ed virtually no uptake activity for both mutation!;. Our data indicate that mutations in OCTN2 are responsible for CDSP. Identification of the underly ing gene in this disease will allow rapid detection of carriers and postnat al diagnosis of affected patients.