Journal of Inherited Metabolic Disease

, Volume 33, Issue 1, pp 33–42

Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population

Authors

  • Erin M. Coffee
    • Biology DepartmentBoston University
  • Laura Yerkes
    • Biochemistry and Molecular Biology ProgramBoston University
  • Elizabeth P. Ewen
    • Biology DepartmentBoston University
  • Tiffany Zee
    • Biochemistry and Molecular Biology ProgramBoston University
    • Department of Genetics and Development, College of Physicians and SurgeonsColumbia University
    • Biology DepartmentBoston University
    • Biochemistry and Molecular Biology ProgramBoston University
Original Article

DOI: 10.1007/s10545-009-9008-7

Cite this article as:
Coffee, E.M., Yerkes, L., Ewen, E.P. et al. J Inherit Metab Dis (2010) 33: 33. doi:10.1007/s10545-009-9008-7

Abstract

Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Δ4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense mutations Δ4E4 and R59Op are the next most common alleles, with each having a frequency of 4%. Together, the frequencies of all seven alleles make up 65% of HFI-causing alleles in this population. Worldwide, these same alleles make up 82% of HFI-causing mutations. This difference indicates that screening for common HFI alleles is more difficult in the American population. Nevertheless, a genetic screen for diagnosing HFI in America can be improved by including all seven alleles studied here. Lastly, identification of HFI patients presenting with classic symptoms and who have homozygous null genotypes indicates that aldolase B is not required for proper development or metabolic maintenance.

Abbreviations

HFI

hereditary fructose intolerance

ASO

allele-specific oligonucleotide

Copyright information

© SSIEM and Springer 2009