Human Genetics

, Volume 105, Issue 1–2, pp 157–161

Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency

  • F.M. Vaz
  • H.R. Scholte
  • J. Ruiter
  • L.M. Hussaarts-Odijk
  • R. Rodrigues Pereira
  • S. Schweitzer
  • J.B.C. de Klerk
  • H.R. Waterham
  • R.J.A. Wanders
Original Investigation
  • 72 Downloads

Abstract

Systemic carnitine deficiency is a potentially lethal, autosomal recessive disorder characterized by cardiomyopathy, myopathy, recurrent episodes of hypoketotic hypoglycemia, hyperammonemia, and failure to thrive. This form of carnitine deficiency is caused by a defect in the active cellular uptake of carnitine, and the gene encoding the high affinity carnitine transporter OCTN2 has recently been shown to be mutated in patients suffering from this disorder. Here, we report the underlying molecular defect in three unrelated patients. Two patients were homozygous for the same missense mutation 632A→G, which changes the tyrosine at amino acid position 211 into a cysteine (Y211C). The third patient was homozygous for a nonsense mutation, 844C→T, which converts the arginine at amino acid position 282 into a stop codon (R282X). Reintroduction of wild-type OCTN2 cDNA into fibroblasts of the three patients by transient transfection restored the cellular carnitine uptake, confirming that mutations in OCTN2 are the cause of systemic carnitine deficiency.

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Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • F.M. Vaz
    • 1
  • H.R. Scholte
    • 2
  • J. Ruiter
    • 1
  • L.M. Hussaarts-Odijk
    • 2
  • R. Rodrigues Pereira
    • 3
  • S. Schweitzer
    • 4
  • J.B.C. de Klerk
    • 5
  • H.R. Waterham
    • 1
  • R.J.A. Wanders
    • 1
  1. 1.Laboratory for Genetic Metabolic Diseases (F0–224), Departments of Clinical Chemistry and Paediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE AmsterdamThe Netherlands
  2. 2.Department of Biochemistry, Cardiovascular Research Institute COEUR, Erasmus University, PO Box 1738, 3000 DR RotterdamThe Netherlands
  3. 3.Department of Paediatrics, St. Clara Hospital, Olympiaweg 350, 3078 HT RotterdamThe Netherlands
  4. 4.Children's Hospital, Hannover Medical School, Carl-Neuberg Str. 1, D-30623 HannoverGermany
  5. 5.Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ RotterdamThe Netherlands

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