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. 2014 May 22:1:241-248.
doi: 10.1016/j.ymgmr.2014.04.008. eCollection 2014.

Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency

Jan Rasmussen  1 , Allan M Lund  2 , Lotte Risom  2 , Flemming Wibrand  2 , Hannes Gislason  3 , Olav W Nielsen  4 , Lars Køber  5 , Morten Duno  2
Affiliations

Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency

Jan Rasmussen et al. Mol Genet Metab Rep. .

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Results: Four different mutations, including the unpublished c.131C 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.

Keywords: OCTN2; Primary carnitine deficiency; SLC22A5; The Faroe Islands.

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Figures

Fig. 1
Fig. 1
OCTN2 activities plotted against free carnitine levels in four different PCD genotypes.
Fig. 2
Fig. 2
Mean fibroblast carnitine uptake activity plotted against mean free carnitine levels in different genotypes, c.95A > G heterozygotes and subjects without PCD (wildtype/wildtype).
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