hereditary fructose intolerance

Fructose intolerance becomes apparent in infancy at the time of weaning, when fructose or sucrose is added to the diet. Clinical features include recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal.

Long-term exposure to fructose can result in liver failure, renal tubulopathy, and growth retardation. Older patients who survive infancy develop a natural avoidance of sweets and fruits.

Hereditary fructose intolerance is caused by mutation in the gene encoding aldolase B (ALDOB; MIM.612724).

Physiopathology

In aldolase B-deficient tissues, cytoplasmic accumulation of fructose-1-phosphate leads to sequestration of inorganic phosphate with resulting activation of AMP deaminase that catalyzes the irreversible deamination of AMP to IMP (inosine monophosphate), a precursor of uric acid.

In the cytoplasm, AMP, ADP, and ATP are maintained in a state approaching equilibrium.

Depletion of tissue ATP occurs through massive degradation to uric acid and impairment of regeneration by oxidative phosphorylation in the mitochondria because of inorganic phosphate depletion. In the cell, ATP exists largely as a 1:1 complex with magnesium.

Depletion of ATP in tissues leads to depletion also of magnesium concentration.