Abstract
The present study provides a retrospective overview of the cohort of phenylketonuria (PKU) patients in Estonia. Based on the available data, the patients clearly cluster into two distinct groups: the patients with late diagnosis and start of therapy (N = 46), who were born before 1993 when the national newborn screening programme was launched, and the screened babies (N = 48) getting their diagnoses at least in a couple of weeks after birth.
Altogether 153 independent phenylalanine hydroxylase (PAH) alleles from 92 patients were analysed in the study, wherein 80% of them were carrying the p.Arg408Trp variation, making the relative frequency of this particular variation one of the highest known. Additionally, 15 other different variations in the PAH gene were identified, each with very low incidence, providing ground for phenotypic variability and potential response to BH4 therapy. Genealogical analysis revealed some “hotspots” of the origin of the p.Arg408Trp variation, with especially high density in South-East Estonia. According to our data, the incidence of PKU in Estonia is estimated as 1 in 6,700 newborns.
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Acknowledgements
The current study has been supported by grant PUT0355 from the Estonian Science Foundation.
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Communicated by: Nenad Blau, PhD
Electronics Supplementary Material
Supplementary Data 1
Details of statistical analysis (DOC 22 kb)
Supplementary Table 1
Relative impact of geographically distinct regions of Estonia (counties) to historical formation of Estonian pool of PAH alleles carrying the p.R408W mutation (DOC 42 kb)
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Synopsis
The retrospective overview of Estonian phenylketonuria (PKU) patients revealed that the incidence of PKU in Estonia is 1 in 6,700 newborns with exceptionally high genetic homogeneity, as 80% of all PKU alleles carry the p.Arg408Trp variation typical for Eastern Europe; the genealogical part of the study disclosed certain regions of the country, where said variation was of higher prevalence compared to whole Estonia.
Author Contribution
All the listed authors have contributed to planning, conduct, and writing of the study; the statistical analysis was carried out by Dr. Tõnu Möls.
Guarantor
We declare Prof Katrin Õunap, MD, PhD as guarantor of this study.
Conflict of Interest
Hardo Lilleväli, Karit Reinson, Kai Muru, Kristi Simenson, Ülle Murumets, Tõnu Möls and Katrin Õunap declare that they have no conflict of interest. None of the authors received remunerations or honorariums of any manner or have any relationship that could inappropriately influence results. During the past 5 years the following authors have obtained reimbursement for attending a symposium/conference: K. Õunap (Biomarine, Sanofi, Shire); K. Reinson (Shire), K. Muru (Biomarine, Nutricia, Shire); K. Simenson (Shire).
Compliance with Ethical Standards
This study was approved by Research Ethics Committee of the University of Tartu (approval date 21.09.2015 number 251/T-6). The approval includes obligatory informed consent from all subjects whose personal or genealogical data has been used in the study.
Animal Rights
This article does not contain any studies with human or animal subjects performed by any of the authors.
Funding
The current study has been supported by grant PUT0355 from the Estonian Science Foundation.
Compliance with Ethics Guidelines
This study was approved by Research Ethics Committee of the University of Tartu (approval date 21.09.2015 number 251/T-6).
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Lilleväli, H. et al. (2017). Hyperphenylalaninaemias in Estonia: Genotype–Phenotype Correlation and Comparative Overview of the Patient Cohort Before and After Nation-Wide Neonatal Screening. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 40. JIMD Reports, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_61
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DOI: https://doi.org/10.1007/8904_2017_61
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