Carnitine uptake defect: frameshift mutations in the human plasmalemmal carnitine transporter gene

Biochem Biophys Res Commun. 1998 Nov 18;252(2):396-401. doi: 10.1006/bbrc.1998.9679.


The genetic defect associated with carnitine uptake is characterized by progressive infantile-onset carnitine responsive cardiomyopathy, weakness, recurrent hypoglycemic hypoketotic encephalopathy, and failure to thrive. The cDNA encoding the sodium ion-dependent, high-affinity human carnitine transporter (557 amino acids) has been recently cloned and mapped to human chromosome 5q31. We herein report the first molecular characterization of the mutations responsible for the carnitine uptake defect in two unrelated patients. RT-PCR analysis of patient lymphoblasts and fibroblasts followed by sequencing of PCR products and their subclones revealed frameshift mutations in the plasmalemmal carnitine transporter. In both patients, the abnormal transcripts showed a partial cDNA deletion of nucleotides 255-1649 resulting in a predicted truncated protein of 92 amino acids. Both patients are compound heterozygotes; in one patient the second mutant allele revealed a 19-bp insertion between nucleotides 874 and 875 resulting in a frameshift yielding a predicted truncated protein of 284 amino acids, while in the second patient the second mutant allele had a deletion of nucleotides 875-1046 resulting in a predicted truncated protein of 237 amino acids.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Biological Transport, Active
  • Carnitine / administration & dosage
  • Carnitine / metabolism*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Female
  • Frameshift Mutation*
  • Humans
  • Kinetics
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Metabolism, Inborn Errors / drug therapy
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism
  • Molecular Sequence Data
  • Organic Cation Transport Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Solute Carrier Family 22 Member 5


  • Carrier Proteins
  • DNA Primers
  • DNA, Complementary
  • Membrane Proteins
  • Organic Cation Transport Proteins
  • SLC22A5 protein, human
  • Solute Carrier Family 22 Member 5
  • Carnitine