What Is Hereditary Fructose Intolerance?

Hereditary fructose intolerance, also known as fructose-1,6-bisphosphate aldolase deficiency, is a serious disease that occurs when infants begin to contain fructose. It is caused by aldolization in the liver, kidney, and small intestine. Caused by lack of enzyme B activity. Fructose-1,6-diphosphate aldolase catalyzes the hydrolysis of fructose-1,6-diphosphate to triose phosphate and glyceraldehyde phosphate. The lack of this enzyme activity leads to rapid accumulation of fructose-1-phosphate in the body after the patient has absorbed fructose, causing severe symptoms of toxicity.

Qiu Wenjuan

(Chief physician)

Department of Pediatrics, Shanghai Xinhua Hospital

Hereditary fructose intolerance, also known as fructose-1,6-bisphosphate aldolase deficiency, is a serious disease that occurs when infants begin to contain fructose. It is caused by aldolization in the liver, kidney, and small intestine. Caused by lack of enzyme B activity. Fructose-1,6-diphosphate aldolase catalyzes the hydrolysis of fructose-1,6-diphosphate to triose phosphate and glyceraldehyde phosphate. The lack of this enzyme activity leads to rapid accumulation of fructose-1-phosphate in the body after the patient has absorbed fructose, causing severe symptoms of toxicity.

On May 11, 2018, the National Health Commission and other five departments jointly formulated the "First Batch of Rare Diseases", and hereditary fructose intolerance was included. ^[1]

Western Medicine Name

Hereditary fructose intolerance

Affiliated Department

Gynecology and Pediatrics-

The main symptoms

Jaundice, liver

Main cause

Genetic metabolic disease

Multiple groups

child

Contagious

Non-contagious

Epidemiology and genetics of hereditary fructose intolerance

The exact incidence of hereditary fructose intolerance is unclear and may be higher than 1/23 000. The gene encoding aldolase B is located at 9q22.3, and several mutations causing the disease have been discovered. One of the most common mutations in Northern Europe is a deliberate mutation, in which G at exon 5 is converted to C, causing alanine at position 149 to be replaced by proline. This mutation and the other two mutations account for 80-85% of the entire mutant allele in Europe and the United States. Inherited fructose intolerance can be diagnosed by direct DNA analysis, and prenatal diagnosis can be performed by DNA mutation analysis or linkage analysis of amniotic fluid and chorion.

Clinical manifestations of hereditary fructose intolerance

Patients with hereditary fructose intolerance do not have any clinical symptoms before absorbing fructose or sucrose (usually from fruits, juices or saccharified cereals). If newborns take foods or formulas containing these sugars immediately after birth, the child will soon develop symptoms. Early clinical manifestations are similar to galactosemia, including jaundice, liver enlargement, vomiting, malaise, irritability, and convulsions. Laboratory tests include prolonged clotting time, hypoalbuminemia, elevated bilirubin transaminase, and proximal tubule dysfunction. Acute fructose intake can cause symptoms of hypoglycemia; long-term intake of fructose can cause growth retardation and liver disease. If continued intake of fructose, hypoglycemia symptoms recur, liver and kidney failure progress, and eventually the patient will die.

Diagnosis of hereditary fructose intolerance

When reducing substances are present in the urine, hereditary fructose intolerance is highly suspected. Intravenous injection of fructose causes a rapid decline in serum phosphate followed by a rapid decrease in blood glucose, followed by an increase in serum uric acid and blood magnesium to support the diagnosis of fructose intolerance. Because patients may develop an acute onset of oral fructose, oral glucose tolerance tests should not be performed on suspected patients. The exact diagnosis depends on the detection of aldolase B activity in liver tissue. ^[2]

Treatment of hereditary fructose intolerance

Sucrose, fructose, and sorbitol should be completely removed from the patient's diet. Because these sugars are often used as additives and even most drugs are present, it may be difficult to completely remove them. After starting treatment, the patient's liver and kidney function improved, and there was catch-up growth. Intellectual development is generally unaffected. In adulthood, symptoms are mild even if the patient ingests fructose. The patient's long-term prognosis is good. Because sucrose is avoided in the diet, patients have almost no dental caries. ^[3]