Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency
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 c...
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ftdoajarticles:oai:doaj.org/article:941f6e69d60f4779a296692eeddb5c80 2023-05-15T16:10:35+02:00 Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency Jan Rasmussen Allan M. Lund Lotte Risom Flemming Wibrand Hannes Gislason Olav W. Nielsen Lars Køber Morten Duno 2014-01-01T00:00:00Z https://doi.org/10.1016/j.ymgmr.2014.04.008 https://doaj.org/article/941f6e69d60f4779a296692eeddb5c80 EN eng Elsevier http://www.sciencedirect.com/science/article/pii/S2214426914000366 https://doaj.org/toc/2214-4269 2214-4269 doi:10.1016/j.ymgmr.2014.04.008 https://doaj.org/article/941f6e69d60f4779a296692eeddb5c80 Molecular Genetics and Metabolism Reports, Vol 1, Iss C, Pp 241-248 (2014) Primary carnitine deficiency OCTN2 SLC22A5 The Faroe Islands Medicine (General) R5-920 Biology (General) QH301-705.5 article 2014 ftdoajarticles https://doi.org/10.1016/j.ymgmr.2014.04.008 2022-12-31T09:00:39Z 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 Results: Four different mutations, including the unpublished c.131C 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. Article in Journal/Newspaper Faroe Islands Directory of Open Access Journals: DOAJ Articles Faroe Islands Molecular Genetics and Metabolism Reports 1 241 248 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Primary carnitine deficiency OCTN2 SLC22A5 The Faroe Islands Medicine (General) R5-920 Biology (General) QH301-705.5 |
spellingShingle |
Primary carnitine deficiency OCTN2 SLC22A5 The Faroe Islands Medicine (General) R5-920 Biology (General) QH301-705.5 Jan Rasmussen Allan M. Lund Lotte Risom Flemming Wibrand Hannes Gislason Olav W. Nielsen Lars Køber Morten Duno Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
topic_facet |
Primary carnitine deficiency OCTN2 SLC22A5 The Faroe Islands Medicine (General) R5-920 Biology (General) QH301-705.5 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Jan Rasmussen Allan M. Lund Lotte Risom Flemming Wibrand Hannes Gislason Olav W. Nielsen Lars Køber Morten Duno |
author_facet |
Jan Rasmussen Allan M. Lund Lotte Risom Flemming Wibrand Hannes Gislason Olav W. Nielsen Lars Køber Morten Duno |
author_sort |
Jan Rasmussen |
title |
Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
title_short |
Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
title_full |
Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
title_fullStr |
Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
title_full_unstemmed |
Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
title_sort |
residual octn2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency |
publisher |
Elsevier |
publishDate |
2014 |
url |
https://doi.org/10.1016/j.ymgmr.2014.04.008 https://doaj.org/article/941f6e69d60f4779a296692eeddb5c80 |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands |
genre_facet |
Faroe Islands |
op_source |
Molecular Genetics and Metabolism Reports, Vol 1, Iss C, Pp 241-248 (2014) |
op_relation |
http://www.sciencedirect.com/science/article/pii/S2214426914000366 https://doaj.org/toc/2214-4269 2214-4269 doi:10.1016/j.ymgmr.2014.04.008 https://doaj.org/article/941f6e69d60f4779a296692eeddb5c80 |
op_doi |
https://doi.org/10.1016/j.ymgmr.2014.04.008 |
container_title |
Molecular Genetics and Metabolism Reports |
container_volume |
1 |
container_start_page |
241 |
op_container_end_page |
248 |
_version_ |
1765995762314903552 |