摘要：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 Results Four different mutations, including the unpublished c.131C 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). Conclusion 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.
关键词：Primary carnitine deficiency; OCTN2; SLC22A5; The Faroe Islands
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