Aldolase B - Pathology

Pathology

Genetic mutations leading to defects in aldolase B result in a condition called hereditary fructose intolerance. Due to the lack of functional aldolase B, organisms with HFI cannot properly process F1P, which leads to an accumulation of F1P in bodily tissues. In addition to being toxic to cellular tissues, high levels of F1P traps phosphate in an unusable form that does not return to the general phosphate pool, resulting in depletion of both phosphate and ATP stores. The lack of readily available phosphate causes the cessation of glycogenolysis in the liver, which results in hypoglycemia. This accumulation also inhibits gluconeogenesis, further reducing the amount of readily available glucose. The loss of ATP leads to a multitude of problems including inhibition of protein synthesis and hepatic and renal dysfunction. Patient prognosis, however, is good in cases of hereditary fructose intolerance. By avoiding foods containing fructose, sucrose, and sorbitol, patients can live symptom-free lives.

HFI is recessively inherited autosomal disorder. Approximately 30 mutations that cause HFI have been identified, and these combined mutations result in a HFI frequency of 1 in every 20,000 births. Mutant alleles are a result of a number different types of mutations including base pair substitutions and small deletions. The most common mutation is A149P, which is a guanine to cytosine transversion in exon 5, resulting in the replacement of alanine at position 149 with proline. This specific mutant allele is estimated to account for 53% of HFI alleles. Other mutations resulting in HFI are less frequent and oftentimes correlated with ancestral origins.