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. 1996 Oct;33(10):837–841. doi: 10.1136/jmg.33.10.837

Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population.

C L James 1, P Rellos 1, M Ali 1, A F Heeley 1, T M Cox 1
PMCID: PMC1050763  PMID: 8933337

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ali M., Rosien U., Cox T. M. DNA diagnosis of fatal fructose intolerance from archival tissue. Q J Med. 1993 Jan;86(1):25–30. [PubMed] [Google Scholar]
  2. Brooks C. C., Tolan D. R. Association of the widespread A149P hereditary fructose intolerance mutation with newly identified sequence polymorphisms in the aldolase B gene. Am J Hum Genet. 1993 Apr;52(4):835–840. [PMC free article] [PubMed] [Google Scholar]
  3. CHAMBERS R. A., PRATT R. T. Idiosyncrasy to fructose. Lancet. 1956 Aug 18;271(6938):340–340. doi: 10.1016/s0140-6736(56)92196-1. [DOI] [PubMed] [Google Scholar]
  4. Cox T. M. Aldolase B and fructose intolerance. FASEB J. 1994 Jan;8(1):62–71. doi: 10.1096/fasebj.8.1.8299892. [DOI] [PubMed] [Google Scholar]
  5. Cross N. C., Cox T. M. Molecular analysis of aldolase B genes in the diagnosis of hereditary fructose intolerance in the United Kingdom. Q J Med. 1989 Nov;73(271):1015–1020. [PubMed] [Google Scholar]
  6. Cross N. C., Tolan D. R., Cox T. M. Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation. Cell. 1988 Jun 17;53(6):881–885. doi: 10.1016/s0092-8674(88)90349-2. [DOI] [PubMed] [Google Scholar]
  7. Cross N. C., de Franchis R., Sebastio G., Dazzo C., Tolan D. R., Gregori C., Odievre M., Vidailhet M., Romano V., Mascali G. Molecular analysis of aldolase B genes in hereditary fructose intolerance. Lancet. 1990 Feb 10;335(8685):306–309. doi: 10.1016/0140-6736(90)90603-3. [DOI] [PubMed] [Google Scholar]
  8. Hardy G. H. MENDELIAN PROPORTIONS IN A MIXED POPULATION. Science. 1908 Jul 10;28(706):49–50. doi: 10.1126/science.28.706.49. [DOI] [PubMed] [Google Scholar]
  9. Mistry P. K., Smith S. J., Ali M., Hatton C. S., McIntyre N., Cox T. M. Genetic diagnosis of Gaucher's disease. Lancet. 1992 Apr 11;339(8798):889–892. doi: 10.1016/0140-6736(92)90928-v. [DOI] [PubMed] [Google Scholar]
  10. Odièvre M., Gentil C., Gautier M., Alagille D. Hereditary fructose intolerance in childhood. Diagnosis, management, and course in 55 patients. Am J Dis Child. 1978 Jun;132(6):605–608. doi: 10.1001/archpedi.1978.02120310069014. [DOI] [PubMed] [Google Scholar]

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