title: Should newborn mutation scanning for hyperphenylalaninaemia and galactosaemia be implemented? A Polish experience.
abstract: OBJECTIVE
  To elucidate whether screening for mutations causing hyperphenylalaninaemia (HPA) and classic galactosaemia could provide important, additional information on a clinical phenotype.
  
  
  METHODS
  Genotypes that cause disease at the phenylalanine hydroxylase (PAH) gene and galactose-1-phosphate uridyltransferase (GALT) gene in a group of 101 hyperphenylalaninaemic and 77 patients with classic galactosaemia were established. The PAH and GALT mutations were identified in genomic DNA extracted from whole blood leucocytes using single stranded conformational analysis and direct fluorescent sequencing of polymerase chain reaction (PCR) products.
  
  
  RESULTS
  Mild HPA and mild phenylketonurea (PKU) were caused by divergent genotypes. In the studied group a total of 26 different mild and intermediate PAH mutations were identified, most of them being rare ones. Classic galactosaemia was caused by two frequent mutations, accounting for 82% of all mutated alleles.
  
  
  CONCLUSIONS
  Identification of mild or intermediate mutations causing HPA could provide fast and reliable information about future clinical outcome of a newborn infant. Molecular diagnosis of HPA should be preceded by biochemical analysis and implemented to differentiate mild forms of HPA and cases of ambiguous classification. Because of multiple rare mutations scattered on all exons, scanning of the entire PAH coding sequence could be useful and cost beneficial. Routine genotyping is not proposed in classic phenylketonuria and classic galactosaemia, as it provides limited additional, prospective information on the clinical phenotype.
authors.affiliation: Department of Medical Genetics, National Research Institute of Mother and Child, Warszawa, Poland. czarekz@iimcb.gov.pl
authors.forename: C
authors.initials: C
authors.lastname: Zekanowski
authors.forename: M
authors.initials: M
authors.lastname: Nowacka
authors.forename: B
authors.initials: B
authors.lastname: Radomyska
authors.forename: B
authors.initials: B
authors.lastname: Cabalska
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005693:Galactosemias / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D015997:Neonatal Screening; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000175:diagnosis / Q000235:genetics*; D011044:Poland; D011237:Predictive Value of Tests; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics
chemical_list: D010651:Phenylalanine Hydroxylase; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase