Epidemiological aspects of hereditary fructose intolerance: A database study

Area of Science:

• Genetics
• Metabolic Disorders
• Human Physiology

Background:

• Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by ALDOB gene variants, leading to aldolase B deficiency.
• Clinical manifestations include hypoglycemia, vomiting, nausea, hepatomegaly, and liver/kidney dysfunction.
• Dietary management with fructose restriction leads to a favorable prognosis.

Purpose of the Study:

• To analyze the distribution of ALDOB variants in HFI patients.
• To estimate HFI prevalence using carrier frequency data from the gnomAD database.
• To assess the utility of in silico predictions for identifying pathogenic variants.

Main Methods:

• Systematic review of ALDOB gene variants in HFI patients.
• Carrier frequency estimation using gnomAD database.
• Inclusion of rare, in silico-predicted pathogenic variants for prevalence calculation.

Main Results:

• The p.(Ala150Pro) and p.(Ala175Asp) variants are the most common ALDOB variants globally, with specific European distribution patterns.
• Estimating HFI prevalence by including rare pathogenic alleles provides more informative data, especially for populations with limited patient numbers.
• The estimated global prevalence of HFI is approximately 1:10,000.

Conclusions:

• HFI is a widely distributed metabolic disorder with a significant global prevalence.
• ALDOB variant analysis, including rare alleles, is crucial for accurate HFI prevalence estimation.
• Understanding variant distribution aids in genetic counseling and public health strategies for HFI.