Novel OCTN2 mutations: No genotype-phenotype correlations: Early carnitine therapy prevents cardiomyopathy

Anne Marie Lamhonwah, Simon E. Olpin, Rodney J. Pollitt, Christine Vianey-Saban, Priscille Divry, Nathalie Guffon, Guy T N Besley, Russell Onizuka, Linda J. De Meirleir, Ljerka Cvitanovic-Sojat, Ivo Baric, Carlo Dionisi-Vici, Ksenija Fumic, Miljenka Maradin, Ingrid Tein

Research output: Contribution to journalArticlepeer-review


Primary systemic carnitine deficiency or carnitine uptake defect (OMIM 212140) is a potentially lethal, autosomal recessive disorder characterized by progressive infantile-onset cardiomyopathy, weakness, and recurrent hypoglycemic hypoketotic encephalopathy, which is highly responsive to L-carnitine therapy. Molecular analysis of the SLC22A5 (OCTN2) gene, encoding the high-affinity carnitine transporter, was done in 11 affected individuals by direct nucleotide sequencing of polymerase chain reaction products from all 10 exons. Carnitine uptake (at Km of 5 μM) in cultured skin fibroblasts ranged from 1% to 20% of normal controls. Eleven mutations (delF23, N32S, and one 11-bp duplication in exon 1; R169W in exon 3; a donor splice mutation [IVS3+1 G>A] in intron 3; frameshift mutations in exons 5 and 6; Y401X in exon 7; T440M, T468R and S470F in exon 8) are described. There was no correlation between residual uptake and severity of clinical presentation, suggesting that the wide phenotypic variability is likely related to exogenous stressors exacerbating carnitine deficiency. Most importantly, strict compliance with carnitine from birth appears to prevent the phenotype.

Original languageEnglish
Pages (from-to)271-284
Number of pages14
JournalAmerican Journal of Medical Genetics
Issue number3
Publication statusPublished - Aug 15 2002


  • Carnitine transporter
  • Cultured skin fibroblasts
  • Fatty acid oxidation
  • Hypertrophic cardiomyopathy
  • Organic cation transporter

ASJC Scopus subject areas

  • Genetics(clinical)


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