JIMD Reports, Volume 40

Hardo Lilleväli, Karit Reinson, Kai Muru, Kristi Simenson, Ülle Murumets, Tõnu Möls, Katrin Õunap, Lilleväli, Hardo, Reinson, Karit, Muru, Kai, Simenson, Kristi, Murumets, Ülle, Möls, Tõnu, Õunap, Katrin

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.