title: Different presentations of late-detected phenylketonuria in two brothers with the same R408W/R111X genotype in the PAH gene.
abstract: Although the clinical heterogeneity of phenylketonuria (PKU) is well established, some questions about this condition remain. Subjects from the same family who share the same mutations in the phenylalanine hydroxylase (PAH) gene are expected to display similar disease courses, and therefore, when blood phenylalanine (Phe) levels, genotype and dietary treatment are all similar, differences in patient outcomes require additional explanations. The present authors describe two entirely different courses of late-detected PKU in two brothers with the same R408W/R111X genotype in the PAH gene. The older sibling was diagnosed with PKU at the age of 4 years and given treatment. His IQ was 97 at 26 years of age and moderate involvement of periventricular white matter was detected. The younger brother was diagnosed with PKU at the age of 11 months and given treatment. His IQ was < 25 at 22 years of age and severe dysmyelination changes were found by magnetic resonance imaging. The differences in the courses of the disease between these two brothers appear to be related to variations in their blood-brain barriers.
authors.affiliation: II Department of Paediatrics, Pomeranian Academy of Medicine, Szczecin, Poland. gizewski@px.pl
authors.forename: M
authors.initials: M
authors.lastname: Gizewska
authors.forename: B
authors.initials: B
authors.lastname: Cabalska
authors.forename: L
authors.initials: L
authors.lastname: Cyrytowski
authors.forename: P
authors.initials: P
authors.lastname: Nowacki
authors.forename: C
authors.initials: C
authors.lastname: Zekanowski
authors.forename: M
authors.initials: M
authors.lastname: Walczak
authors.forename: I
authors.initials: I
authors.lastname: Jóźwiak
authors.forename: D
authors.initials: D
authors.lastname: Koziarska
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D013997:Time Factors
chemical_list: D010651:Phenylalanine Hydroxylase