fructose What we need to know

01.09.2023

Fructosuria is a condition developed as a result of disruption of fructose metabolism, when the concentration of fructose in the urine and blood increases. The reason for this may be genetic mutations - during which a deficiency of fructose-converting enzymes develops.

There are three variants of genetic disorders of fructose metabolism:

Essential fructosuria – fructokinase deficiency
Hereditary fructose intolerance - fructose-1-phosphate aldolase
Hereditary deficiency of fructose-1.6-biphosphatase

Essential fructose is a mild disease and does not require treatment. The condition is characterized by an increase in the concentration of fructose in the urine after the infant starts feeding. This condition is the result of deficiency of the liver enzyme - fructokinase (the same as ketohexokinase) and is an autosomal recessive genetic pathology. In the case of deficiency of the enzyme fructokinase, fructose is metabolized with the participation of the enzyme hexokinase into fructose-6-phosphate, in the metabolism of which other enzymes are involved. That is why fructosuria developed during fructokinase deficiency is a benign condition and does not require treatment.

Hereditary fructose intolerance is the inability to digest fructose (fruit sugar). The reason for this is insufficient activity of its converting enzyme - fructose-1-phosphate aldolase. This leads to the accumulation of fructose-1-phosphate in the liver, kidney, and wall of the small intestine. This can lead to life-threatening complications, especially in infants. People with hereditary fructose intolerance have a strong aversion to sweets and fruits. After eating such products, abdominal pain, nausea, vomiting, hypoglycemia (low blood sugar) occur.

Early diagnostics is important because by following a fructose-free diet, such people can lead a normal life. Without treatment, such complications as liver and kidney failure, malabsorption-malnutrition and related pathologies develop.

Symptoms

As soon as fructose-containing products are included in the baby's diet, symptoms appear soon:

Prolonged vomiting
Delay in physical development
Weakness
Jaundice
Liver enlargement and sometimes cirrhosis
Propensity to bleeding from the gastrointestinal tract due to deficiency of clotting factors
Episodes of altered consciousness
Decreased blood glucose and phosphate levels and increased blood and urine fructose concentrations
malabsorption-malnutrition

reasons

Hereditary fructose intolerance is an autosomal recessive genetic pathology, the determining gene of which is located on the long arm of the 9th chromosome in the 9q22.3 locus. A recessive disease occurs when a person inherits the same pathological gene from both parents. If such a gene is received from only one parent, and the other gene is healthy, this person will be the carrier of this mutated gene. The disease will not be detected in it.

If both parents carry the abnormal gene, each pregnancy has a 25% risk of giving birth to a child with the disease, a 50% risk of giving birth to a child carrying the mutation, and a 25% risk of giving birth to a healthy child. The risk equally covers female and male sex.

Every person can be a carrier of several pathological (mutated) genes. If a couple is closely related by blood, with a high probability of carrying the same genes, the risk of developing this or that disease in their offspring is much higher.

Hereditary fructose intolerance is diagnosed at birth, or soon after the start of feeding. The frequency of the disease is 1:10-000 in live births.

Hereditary deficiency of fructose-1.6-biphosphatase inhibits the metabolism of glycogen in the liver, which is the body's energy reserve. As a result, the patient develops hypoglycemia (a decrease in the level of sugar in the blood), hyperventilation, ketosis (due to the accumulation of breakdown intermediates in the blood) and lactic acidosis. Without treatment, this condition is life-threatening, especially in newborns.

Diagnosis

Diagnosis is based on the study of enzymes and their activity, which is carried out by liver biopsy, is an invasive (aggressive) procedure and is associated with certain risks, especially in newborns.

Non-invasive screening of newborns by determining the concentration of metabolites in urine, including fructose, is considered the gold standard of diagnostics. The advantage of the method is its simplicity.