Inability to use dietary fructose; a rare genetic disease of fructose metabolism. Three hereditary diseases result from a mutation in one of three key enzymes of fructose metabolism: (1) fructokinase, (2) aldolase B, and (3) fructose 1,6-bisphosphatase. A mutation in the gene for fructokinase is characterized by elevated blood and urine levels of fructose. A second mutation has been identified in the gene for aldolase B. This is the enzyme that catalyzes the splitting of fructose 1-phosphate to glyceraldehyde phosphate and dihydroxyacetone phosphate. Aldolase B is located in the liver only. The mutation is such that the enzyme has a reduced affinity for its substrate, fructose 1-phosphate. The results of this reduced affinity include hypoglycemia due to an inhibition of glycogenolysis by fructose 1-phosphate. This hypoglycemia is not responsive to glucagon stimulation. In addition to the disturbance in glycogenolysis, patients with this disorder vomit after a fructose load; have elevated levels of urine and blood fructose; grow poorly with evidence of jaundice; and have hyperbilirubinemia (high levels of bilirubin in the blood), albuminuria (albumin in the urine), and amino aciduria (amino acids in the urine), and some patients may have damaged renal proximal convoluted tubules.
Inability to metabolize the carbohydrate fructose due to a hereditary absence or deficiency of the enzyme 1,6-biphosphate aldolase B. Clinical signs develop early in life. They include hypoglycemia, jaundice, hepatomegaly, vomiting, lethargy, irritability, and convulsions. Fructose can be identified in the urine. The fructose tolerance test should not be used be cause it can induce irreversible coma.