Pielęgniarstwo i Zdrowie Publiczne

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ISSN 2082-9876 (print)
ISSN 2451-1870 (online)
Periodyczność – kwartalnik

Pobierz oryginał (PL) Pobierz tłumaczenie (EN)

Pielęgniarstwo i Zdrowie Publiczne Nursing and Public Health

2020, tom 10, nr 4, październik-grudzień, str. 277–282

doi: 10.17219/pzp/122026

Typ publikacji: praca poglądowa

Język publikacji: polski

Licencja: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Fenyloketonuria nietypowa – ponad 60 lat badań po odkryciu tetrahydrobiopteryny

Atypical phenylketonuria: Over 60 years from the discovery of tetrahydrobiopterin

Kamil Konrad Hozyasz1,A,B,C,D,E,F

1 Wydział Nauk o Zdrowiu, Państwowa Szkoła Wyższa im. Papieża Jana Pawła II w Białej Podlaskiej, Biała Podlaska, Polska

Streszczenie

Fenyloketonuria po raz pierwszy została opisana i zdefiniowana biochemicznie w 1934 r. przez Norwega Ivara Asbjørna Føllinga. Choroba ta jest dziedziczonym autosomalnie recesywnie zaburzeniem metabolizmu powodowanym przez mutację genu kodującego hydroksylazę fenyloalaninową, przekształcającego fenyloalaninę w tyrozynę. W latach 60. XX w. Guthrie stworzył test przesiewowy w kierunku hiperfenyloalaninemii. Fenyloketonuria stała się pierwszą chorobą diagnozowaną we wczesnym stadium przed wystąpieniem objawów klinicznych dzięki populacyjnemu badaniu przesiewowemu noworodków. Tetrahydrobiopteryna (BH4) jest niezbędnym kofaktorem dla różnych enzymów, w tym hydroksylazy fenyloalaninowej. Poznano heterogenną grupę wrodzonych zaburzeń metabolizmu BH4 bez hiperfenyloalaninemii lub z nią (fenyloketonuria nietypowa). U części chorych na fenyloketonurię klasyczną podaż BH4 przywraca zdolność metabolizowania fenyloalaniny. Odkrycie BH4 przez Kaufmana przed 6 dekadami zaowocowało otwarciem nowych ważnych obszarów badań biologicznych i medycznych.

Abstract

Phenylketonuria was 1st described and defined biochemically in 1934 by Norwegian Ivar Asbjørn Følling. The disease is an autosomal recessive inborn error of metabolism caused by pathogenic variants in the gene encoding the enzyme phenylalanine hydroxylase that normally converts phenylalanine to tyrosine. In the 1960s, a diagnostic test was developed by Guthrie that enabled mass screening for hyperphenylalaninemia, and phenylketonuria became the first disease ever for which early presymptomatic diagnosis was possible due to population-based neonatal screening. The tetrahydrobiopterin (BH4) cofactor is essential for the activity of various enzymes, including phenylalanine hydroxylase. It is a heterogeneous group of inherited disorders in BH4 metabolism, presenting with (atypical phenylketonuria) or without hyperphenylalaninemia. Moreover, BH4 may promote the normal metabolism of phenylalanine in a subset of patients with classic phenylketonuria who are BH4-responsive. Thus, what started 6 decades ago as Kaufman’s discovery of the cofactor, has opened up novel and productive avenues of biological and medical research.

Słowa kluczowe

historia medycyny, fenyloketonuria nietypowa, tetrahydrobiopteryna

Key words

history of medicine, atypical phenylketonuria, tetrahydrobiopterin

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