caa a22 4500 475785797 CHVBK 20180406123657.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/PL00014381 doi (NATIONALLICENCE)springer-10.1007/PL00014381 Mutation analysis anticipates dietary requirements in phenylketonuria [Elektronische Daten] [Fleming Güttler, Per Guldberg] Phenylalanine hydroxylase (PAH) deficiency is inherited as an autosomal recessive trait and the associated hyperphenylalaninaemia phenotype is highly variable, primarily due to a great allelic heterogeneity at the PAH locus (approximately 400 disease-associated mutations are known). The arbitrary classification of PAH deficiency on the basis of clinical parameters has been complicated by the lack of international guidelines, leading to a wide confusion in both methodology and terminology. Recently, significant improvements in methods for detection of mutations have paved the way for an alternative system for classification of PAH deficiency, which is based solely on PAH genotypes. This paper gives a summary of the recent progress made in establishing a direct correlation between individual PAH mutations and biochemical and metabolic phenotypes, including the use of "functionally hemizygous” patients to classify both common and rare mutant alleles, and a simple and general model to predict the combined phenotypic effect of two mutant PAH alleles. Conclusion Genotype-based prediction of the biochemical phenotype is now feasible in the majority of newborns with hyperphenylalaninemia, which may be useful for refining diagnosis and anticipating dietary requirements. A recent observation suggests that the genotype also determines cognitive development if dietary therapy is discontinued at 6 years of age. Springer-Verlag Berlin Heidelberg, 2000 Key words Functional hemizygosity nationallicence Genotype-phenotype correlations nationallicence Mutation nationallicence Phenylalanine hydroxylase nationallicence Phenylketonuria nationallicence AbbreviationsAV assigned value nationallicence MHP mild hyperphenylalaninaemia nationallicence PAH phenylalanine hydroxylase nationallicence Phe phenylalanine nationallicence PKU phenylketonuria nationallicence Güttler Fleming The John F. Kennedy Institute, Gl. Landevej 7, 2600 Glostrup, Denmark e-mail: flg@kennedy.dk Tel.: +45-43-260100; Fax: +45-43-431130, DK aut Guldberg Per The John F. Kennedy Institute, Gl. Landevej 7, 2600 Glostrup, Denmark e-mail: flg@kennedy.dk Tel.: +45-43-260100; Fax: +45-43-431130, DK aut https://doi.org/10.1007/PL00014381 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00014381 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Güttler Fleming The John F. Kennedy Institute, Gl. Landevej 7, 2600 Glostrup, Denmark e-mail: flg@kennedy.dk Tel.: +45-43-260100; Fax: +45-43-431130, DK aut NATIONALLICENCE 700 1- Guldberg Per The John F. Kennedy Institute, Gl. Landevej 7, 2600 Glostrup, Denmark e-mail: flg@kennedy.dk Tel.: +45-43-260100; Fax: +45-43-431130, DK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer