Abstract
The aim of our study was to evaluate the prevalence of long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the general Estonian population and among patients with symptoms suggestive of fatty acid oxidation (FAO) defects. We collected DNA from a cohort of 1,040 anonymous newborn blood spot samples. We screened these samples for the presence of the common c.1528G>C mutation in the HADHA gene. Based on the clinical suspicion of FAO defects, we screened suspected individuals since 2004 for the common c.1528G>C mutation in the HADHA gene and since 2008 in addition by tandem mass spectrometric analysis of plasma acylcarnitines. Our results showed that the carrier frequency of the c.1528G>C mutation in the Estonian population is high – 1:173. During the screening of symptomatic patients, we identified five LCHADD patients in four families. Three patients were retrospectively identified by molecular screening of the HADHA gene. One patient was homozygous for the c.1528G>C mutation in the HADHA gene, and two siblings were compound heterozygotes with HADHA genotype c.[1528G>C]+[1690-2A>G]. Among patients tested using acylcarnitine profiling, we identified two cases with an abnormal acylcarnitine profile typical to LCHADD. Molecular analysis showed homozygosity for c.1528G>C mutation. Based on a carrier frequency of 1:173 (95% Confidence Interval 1:76–1:454) and taking into account that the c.1528G>C mutation makes up 87.5% of disease alleles in Estonian LCHADD patients, the estimated prevalence of LCHADD in Estonia would be 1: 91,700.
Competing interest: None declared.
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Abbreviations
- LCHADD:
-
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
- FAO:
-
Fatty acid oxidation
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Acknowledgements
This research was supported by the Estonian Science Foundation SF0180044s09, SF0182695s05 GARBK 7494 and GARLA 8175 grants. The study by K. Joost in Amsterdam MC in The Netherlands was partly supported by the Archimedes Foundation. We thank Prof. E. Mönch from the Charité-Virchow Klinikum in Berlin, Germany for performing the acylcarnitine analysis. We are grateful to E. Roomets for her technical assistance. We thank David Hougaard of the Department of Clinical Biochemistry and Immunology, Statens Serum Institute in Copenhagen, Denmark for providing dried bloodspots collected from the general Danish population.
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Communicated by: Jerry Vockley.
Appendices
Concise One-Sentence Take-Home Message
The carrier frequency of the c.1528G>C mutation in the HADHA gene in the Estonian population is 1:173.
Abbreviated Title
LCHADD in Estonia
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OMIM #609016
Details of the Contributions Made by Individual Authors
K. Joost – development of method and performance of tandem MS analysis of acylcarnitines of all investigated individuals, diagnosis of suspected and confirmed cases, compilation of manuscript, treatment of a patient with LCHAD deficiency.
K. Õunap – planning of study, selection of suspected cases, moderation of cooperation between different centers, diagnosis of suspected patients, compilation of manuscript
R. Žordania – selection of suspected cases, diagnosis and evaluation of a family with LCHAD deficiency
M.-L. Uudelepp – evaluation and treatment of a patient with LCHAD deficiency
R.K. Olsen – sequencing of HADHA gene
K. Kall – performance of organic acid GC/MS analyses during the confirmation/exclusion of suspected LCHADD cases
K. Kilk – development of tandem MS analysis of acylcarnitines
U. Soomets – planning of strategy for biochemical diagnosis using tandem MS
T. Kahre – performance of molecular analysis for main mutation in HADHA gene in all investigated individuals, compilation of manuscript
Guarantor of Article
Kairit Joost
Statement of Competing Interest
All of the authors confirm that they have no competing interests to declare. There is no financial or nonfinancial interest in publishing this article.
Details of Funding
This work was supported by the SF0180044s09, SF0182695s05 GARBK 7494 and GARLA 8175 grants from the Estonian Science Foundation.
Details of the Ethics Approval
The Ethics Review Committee on Human Research of the University of Tartu approved the study.
Patient Consent Statement
Informed consent was obtained from the parents of the children involved in the research.
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Joost, K. et al. (2011). Prevalence of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency in Estonia. In: JIMD Reports - Case and Research Reports, 2011/2. JIMD Reports, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_51
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DOI: https://doi.org/10.1007/8904_2011_51
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