Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency

Genet Med. Nov-Dec 1998;1(1):34-9. doi: 10.1097/00125817-199811000-00008.


Purpose: Primary carnitine deficiency is an autosomal recessive disorder caused by defective carnitine transport and manifests as nonketotic hypoglycemia or skeletal or heart myopathy.

Methods: To define the mechanisms producing partially reduced plasma carnitine levels in the parents of affected patients, we examined carnitine transport in vivo and in the fibroblasts of a new patient and his heterozygous parents.

Results: Kinetic analysis of carnitine transport in fibroblasts revealed an absence of saturable carnitine transport in the proband's cells and a partially impaired carnitine transport in fibroblasts from both parents, whose cells retained normal Km values toward carnitine (6-9 microM) but reduced Vmax. At steady state, normal fibroblasts accumulated carnitine to a concentration that was up to 80 times the extracellular value (0.5 microM). By contrast, cells from the proband had minimal carnitine accumulation, and cells from both parents had intermediate values of carnitine accumulation. Plasma carnitine levels were slightly below normal in both heterozygous, yet clinically normal, parents and in the paternal grandfather and the maternal grandmother. To define the mechanism producing partially decreased carnitine levels, we studied urinary carnitine losses in heterozygous parents compared with controls. Urinary losses increased linearly (P < 0.05) with plasma carnitine levels in normal controls. When urinary carnitine losses were normalized to plasma carnitine levels, a significant difference was observed between controls and heterozygous individuals (P < 0.01).

Conclusions: These results indicate that fibroblasts from heterozygotes for primary carnitine deficiency have a decreased capacity to accumulate carnitine and that heterozygotes have increased urinary losses, which may contribute to their reduced plasma carnitine levels.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / urine
  • Carnitine / blood
  • Carnitine / deficiency*
  • Carnitine / urine*
  • Heterozygote*
  • Humans
  • Infant, Newborn
  • Kinetics
  • Male


  • Carnitine