Fructose Intolerance: Causes

Pathogenesis (development of disease)

Fructose intolerances (fructose intolerances) include essential fructosuria, hereditary fructose intolerance, and fructose malabsorption. The first two metabolic disorders are caused by various genetic enzyme defects. Fructose malabsorption (intestinal fructose intolerance) is a disorder in the absorption of fructose via the intestine. In essential fructosuria, a genetic defect leads to a loss of activity of the enzyme fructokinase in the liver, resulting in an accumulation of fructose in the blood (fructosemia) and in the urine (fructosuria). As a result, the fructose (fruit sugar) is excreted in the urine due to the filtering processes in the kidney. This metabolic disorder is harmless and does not require treatment. The frequency is about 1:130,000.In contrast, hereditary fructose intolerance is a serious inherited disorder of fructose metabolism. In this case, affected individuals exhibit a deficiency or loss of activity of the enzyme fructose-1-phosphate aldolase B. As a result, another form of the enzyme, which is normally active primarily in muscle, comes to the fore. The fructose can only be broken down insufficiently and accumulates in the blood (fructosemia). In addition, uric acid production is increased (hyperuricemia) and the formation of glucose is disturbed – acidosis (hyperacidity) and hypoglycemia (low blood sugar) are the consequences.This disorder occurs extremely rarely in newborns, in about one in 20,000 cases. If a fructose-sensitive infant is introduced to fructose through complementary foods – fruits, vegetables, juices, honey – typical symptoms such as disturbances of the gastrointestinal tract, hypoglycemia, nausea, vomiting, trembling, sweating, pallor, fatigue, and seizures occur in the first few months of life.If affected infants do not avoid fructose in their diet, the kidneys and liver in particular are severely damaged. If a strict diet is not followed, organ damage continues to increase until liver dysfunction – jaundice (icterus), edema, coagulation disorders – and increased proteinuria (increased excretion of protein in the urine) occur as a result of kidney damage. The treatment of hereditary fructose intolerance is a fructose-, sucrose- and sorbitol-free diet (avoidance of fructose, cane sugar and sorbitol).Intestinal fructose intolerance is caused by disturbed intestinal flora (dysbiosis) as a result of chronic stress – long-term malnutrition, environmental pollution, toxins (e. g. Fructose malabsorption is a defect of the glucose transporter GLUT 5, which leads to an incomplete intestinal fructose absorption. As a result, the transport system in the small intestine and thus the absorption of fructose (fruit sugar) is disturbed in that fructose can no longer be transported through the small intestine into the blood and lymph channels. As a result, about half of those affected suffer from symptoms of varying severity. The symptoms are much milder compared to hereditary fructose intolerance and the reduced fructose absorption can be improved by the simultaneous intake of glucose. Therefore, this case is referred to as malabsorption (malresorption) rather than intolerance.

Etiology (causes)

Biographic causes

  • Genetic burden from parents, grandparents.
  • Hereditary fructose intolerance
    • Loss of activity of the enzyme fructose-1-phosphate aldolase B.
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: ADOB
        • SNP: rs1800546 in the gene ADOB
          • Allele constellation: CG (carrier of hereditary fructose intolerance).
          • Allele constellation: CC (causes hereditary fructose intolerance).
        • SNP: rs76917243 in the gene ADOB.
          • Allele constellation: GT (carrier of hereditary fructose intolerance).
          • Allele constellation: TT (causes hereditary fructose intolerance).
        • SNP: rs78340951 in the gene ADOB
          • Allele constellation: CG (carrier of hereditary fructose intolerance).
          • Allele constellation: GG (causes hereditary fructose intolerance).
        • SNP: rs387906225 in the gene ADOB.
          • Allele constellation: DI (carrier of hereditary fructose intolerance).
          • Allele constellation: DD (causes hereditary fructose intolerance).