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

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

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.

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Abbreviations

HFI:

hereditary fructose intolerance

ASO:

allele-specific oligonucleotide

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Acknowledgements

The authors thank Sarah Kampert, Miho Teruya, Christine Foster, Janet Lau, and Sheri Procious for their technical assistance in the genetic screening and Dr. John Celenza for many helpful discussions.

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  1. Tiffany Zee

    Present address: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, HHSC 1602, New York, NY, 10032, USA

Authors and Affiliations

  1. Biology Department, Boston University, 5 Cummington Street, Boston, MA, 02215, USA

    Erin M. Coffee, Elizabeth P. Ewen & Dean R. Tolan

  2. Biochemistry and Molecular Biology Program, Boston University, Boston, MA, 02215, USA

    Laura Yerkes, Tiffany Zee & Dean R. Tolan

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  1. Erin M. Coffee
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  2. Laura Yerkes
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Correspondence to Dean R. Tolan.

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Communicated by: Douglas A. Brooks

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Coffee, E.M., Yerkes, L., Ewen, E.P. et al. Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. J Inherit Metab Dis 33, 33–42 (2010). https://doi.org/10.1007/s10545-009-9008-7

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