Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Fructose Intolerance, hereditary [E74.1]

OMIM numbers: 229600, 612724 (ALDOB), 611570 (FBP1)

Dipl.-Biol. Birgit Busse

Scientific Background

Hereditary fructose intolerance (HFI) is a severe autosomal recessive metabolic disorder that usually manifests already in infants when they are fed with fructose. Regarding differential diagnosis, HFI has to be distinguished from fructose malabsorption, which is mainly accompanied by gastrointestinal signs and symptoms.

Hereditary fructose intolerance leads to severe clinical signs and symptoms after the intake of fructose. Chronic exposure results in failure to thrive and liver cirrhosis. Affected patients frequently develop aversion against sweet food which may cause the disease to stay latent. Mutations in the aldolase B (ALDOB) gene lead to enzyme deficiency which causes the accumulation of toxic metabolite fructose-1-phosphate after the intake of fructose. This triggers inhibition of gluconeogenesis and glycogenolysis which causes hypoglycemia resulting in tremor, attacks of sweating and comatose states as well as gastrointestinal conditions. Four frequently occurring variants in the ALDOB gene (A149P, A174D, N334K and the stop mutation Y203X) are responsible for approximatly 85% of the HFI cases in the European population; the variants A149P and A174D are the cause in 50% of all cases. Inheritance of the disease is autosomal recessive, i.e. for the enzyme deficiency to cause signs and symptoms both alleles of the gene have to be mutated. With an incidence of approx. 1 in 20,000 among the Western population, the condition is rare.

Hereditary fructose-1,6-bisphosphatase (FBP1) deficiency is another form of fructose intolerance and exhibits similar signs and symptoms to HFI.

If the HFI or the FBP1 deficiency remains undetected and untreated, potentially life-threatening situations and later-on progredient organ damage may occur, especially during infancy. Moreover, the treatment with medication containing fructose, sucrose or sorbitol may cause severe side-effects.