title: Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency.
abstract: BACKGROUND
  The prevalence of primary carnitine deficiency (PCD) in the Faroe Islands is the highest reported in the world (1:300). Serious symptoms related to PCD, e.g. sudden death, have previously only been associated to the c.95A > G/c.95A > G genotype in the Faroe Islands. We report and characterize novel mutations associated with PCD in the Faroese population and report and compare free carnitine levels and OCTN2 transport activities measured in fibroblasts from PCD patients with different genotypes.
  
  
  METHODS
  Genetic analyses were used to identify novel mutations, and carnitine uptake analyses in cultured skin fibroblasts from selected patients were used to examine residual OCTN2 transporter activities of the various genotypes.
  
  
  RESULTS
  Four different mutations, including the unpublished c.131C > T (p.A44V), the novel splice mutation c.825-52G > A and a novel risk-haplotype (RH) were identified in the Faroese population. The two most prevalent genotypes were c.95A > G/RH (1:600) and c.95A > G/c.95A > G (1:1300). Patients homozygous for the c.95A > G mutation had both the significantly (p< 0.01) lowest mean free carnitine level at 2.03 (SD 0.66) μmol/L and lowest residual OCTN2 transporter activity (4% of normal). There was a significant positive correlation between free carnitine levels and residual OCTN2 transporter activities in PCD patients (R2= 0.430,p< 0.01).
  
  
  CONCLUSIONS
  There was a significant positive correlation between carnitine levels and OCTN2 transporter activities. The c.95A > G/c.95A > G genotype had the significantly lowest mean free carnitine level and residual OCTN2 transporter activity.
authors.affiliation: Department of Internal Medicine, National Hospital, FO-100 Torshavn, the Faroe Islands.
authors.forename: Jan
authors.initials: J
authors.lastname: Rasmussen
authors.affiliation: Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Lund
authors.affiliation: Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Risom
authors.affiliation: Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Wibrand
authors.affiliation: Faculty of Natural and Health Sciences, University of the Faroe Islands, Torshavn, the Faroe Islands.
authors.forename: Hannes
authors.initials: H
authors.lastname: Gislason
authors.affiliation: Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Olav W
authors.initials: OW
authors.lastname: Nielsen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
keywords: OCTN2; Primary carnitine deficiency; SLC22A5; The Faroe Islands