Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter

Jun Ichi Nezu, Ikumi Tamai, Asuka Oku, Rikiya Ohashi, Hikaru Yabuuchi, Noriyoshi Hashimoto, Hiroko Nikaido, Yoshimichi Sai, Akio Koizumi, Yutaka Shoji, Goro Takada, Toyojiro Matsuishi, Makoto Yoshino, Hirohisa Kato, Toshihiro Ohura, Gozoh Tsujimoto, Jun Ichiro Hayakawa, Miyuki Shimane, Akira Tsuji

Research output: Contribution to journalArticlepeer-review

504 Citations (Scopus)


Primary systemic carnitine deficiency (SCD; OMIM 212140) is an autosomal recessive disorder characterized by progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonaemia. SCD has also been linked to sudden infant death syndrome. Membrane-physiological studies have suggested a defect of the carnitine transport system in the plasma membrane in SCD patients and in the mouse model, juvenile visceral steatosis (jvs; ref. 6). Although the responsible loci have been mapped in both human and mouse, the underlying gene has not yet been identified. Recently, we cloned and analysed the function of a novel transporter protein termed OCTN2 (ref. 9). Our observation that OCTN2 has the ability to transport carnitine in a sodium- dependent manner prompted us to search for mutations in the gene encoding OCTN2, SLC22A5. Initially, we analysed the mouse gene and found a missense mutation in Slc22a5 in jvs mice. Biochemical analysis revealed that this mutation abrogates carnitine transport. Subsequent analysis of the human gene identified four mutations in three SCD pedigrees. Affected individuals in one family were homozygous for the deletion of a 113bp region containing the start codon. In the second pedigree, the affected individual was shown to be a compound heterozygote for two mutations that cause a frameshift and a premature stop codon, respectively. In an affected individual belonging to a third family, we found a homozygous splice-site mutation also resulting in a premature stop codon. These mutations provide the first evidence that loss of OCTN2 function causes SCD.

Original languageEnglish
Pages (from-to)91-94
Number of pages4
JournalNature Genetics
Issue number1
Publication statusPublished - 01-1999

All Science Journal Classification (ASJC) codes

  • Genetics


Dive into the research topics of 'Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter'. Together they form a unique fingerprint.

Cite this