Carnitine transporter deficiency (CTD) in the Faroe Islands and association to cardiac risk.
01.01.2011 - 17.06.2014
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In recent years it has become apparent that the prevalence of carnitine transporter deficiency (CTD) might be higher in the Faroe Islands than anywhere else in the world. Carnitine transporter deficiency is suspected to have claimed the lives of several young Faroese individuals. However there are many aspects regarding CTD in general that remain a mystery. By taking advantage of the high prevalence of patients and subjects either suffering from CTD or being carriers for CTD in the Faroe Islands, we have an unique opportunity to generate more precise and scientific sound data on this disease.
Firstly, we want to systematically characterize the prevalence of subjects with reduced blood carnitine levels on the Faroe Islands, and to examine the association between genotypes and plasma concentration of carnitine.
Secondly, by studying the fatal cases of young Faroese individuals, their familial and genetic background, we will examine to what degree the cause of death could be ascribed to carnitine transporter deficiency or some other confounding factor, maybe genetic, dietary or unknown.
Thirdly, by a detailed cardiac examination of homozygotes, heterozygotes and a control group, we will study if there is an increased prevalence of cardiac abnormalities in relation to carnitine transporter deficiency and to what degree such cardiac abnormalities may be ascribed to the genotype or plasma concentration of carnitine.
By referring to these 3 study questions, the following proposed hypotheses will be tested: 1. CTD is more common in the Faroese Islands than elsewhere, and the discovered CTD homozygotes are not equally distributed by age. 2.The transport of carnitine over fibroblast plasmalemma is lower for patients homozygous for the c.95A>G mutation compared to the patients with compound heterozygous for c.95A>G and another mutation and individuals heterozygous for c.95A>G. 3. The fatal victims of CTD did not die because of structural heart disorder brought on by CTD. 4. Discovered homozygotes in the Faroe Islands do not present with increased incidence of structural cardiac abnormalities, and the frequency of structural abnormality does not differ between homozygotes, heterozygotes and normal controls.
Preparations for the project were made in 2010. Knowledge regarding PCD was lacking and it was thus imparative to study the disorder in the Faroe Islands. The project started officially in the spring of 2011 and the defence of the thesis was held in June 2014. The project was performed in cooperation with several institutions among others Rigshospitalet and the Faroese Biobank. The main results were that the prevalence of PCD in the Faroe Islands was 1:300. There is a significant difference in carnitine levels between males and females. A lower cut-off value of 5 micromol/L in free carnitine was adequate to find patients with the moste severe PCD genotype (N32S/N32S). Five different mutations associated with PCD were discovered in the Faroese population. Most patients were without serious symptoms when diagnosed with PCD.
Scientific articles, books, thesis etc.
Articles publised in peer-reviewed journals:
1. Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands, 2014, Journal of Inherited Metabolic Disease.
2. Primary Carnitine Deficiency in the Faroe Islands: Health and cardiac status in 76 adult patients diagnosed by screening, 2014, Journal of Inherited Metabolic Disease.
3. Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in patients with primary carnitine deficiency, 2014, Molecular Genetics and Metabolism Reports
Thesis: Primary Carnitine Deficiency in the Faroe Islands – an epidemiological and clinical study (available upon request from the author – and will be made available in the National Library in the Faroe Islands, The National Hospital in the Faroe Islands and likely online at the University of Copenhagen.)
Other results, such as unpublished articles, patents, computer systems, original models and new procedures:
Papers are still pending, which describe results obtained in the project period. The results from the study have given important insights into PCD and aid in the clinical treatment of patients with the disorder.
Publications outside the scientific community, i.e. lectures, periodicals, articles in newspapers, television and radio:<
The main author has regularly been in Faroese media to explain results from the study and matters concerning PCD. The main author has also held several lectures, e.g. in Barcelona this autumn, regarding the topic of PCD.