title: Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population.
abstract: Hereditary fructose intolerance (HFI) causes severe and sometimes fatal metabolic disturbances in infants and children but responds to dietary treatment. To determine the practicability of screening newborn infants for HFI, we have investigated the frequency of the most common and widespread mutant allele of aldolase B, A149P, in the neonatal population. The polymerase chain reaction was used to amplify aldolase B exon 5 genomic sequences in DNA present in dried blood specimens preserved on Guthrie cards. The A149P mutation was identified by discriminatory hybridisation to allele specific oligonucleotides and confirmed independently by digestion with the restriction endonuclease BsaHI. Twenty-seven A149P heterozygotes were identified by the molecular analysis of aldolase B genes in blood samples obtained from a random cohort of 2050 subjects born in 1994 and 1995, 1.32 +/- 0.49% (95% confidence level). Although no A149P homozygotes were identified, the data allow the frequency of 1 in 23,000 homozygotes for this allele to be predicted. Our findings have implications for establishing an interventional mass screening programme to identify newborn infants with HFI in the UK.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: James
authors.forename: P
authors.initials: P
authors.lastname: Rellos
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: A F
authors.initials: AF
authors.lastname: Heeley
authors.forename: T M
authors.initials: TM
authors.lastname: Cox
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D005633:Fructose Intolerance / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000097:blood / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening; D011153:Population; D006113:United Kingdom
chemical_list: D005634:Fructose-Bisphosphate Aldolase