Hereditary fructose intolerance

Classification according to ICD-10
E74.1	Disorders of the fructose metabolism Fructose-1,6-bisphosphatase deficiency Hereditary fructose intolerance
ICD-10 online (WHO version 2019)

Hereditary fructose intolerance (HFI) is a rare disease caused by a hereditary disorder of the fructose metabolism, in which the fructose-1-phosphate formed from fructose (fruit sugar) can not be broken down or in sufficient quantities. As a result, the fructose content in the cells is increased with a toxic effect, which in turn disrupts the metabolism of glucose and causes hypoglycaemia. It must not be confused with the much more common intestinal fructose intolerance due to fructose malabsorption. The frequency of annual diseases per 100,000 people ( incidence ) of hereditary fructose intolerance is 1: 10,000 to 1: 130,000, while fructose malabsorption affects around 30–40% of Central Europeans, around half of them with symptoms.

Mode of action

Entry of fructose into glycolysis.
Fructose (1), Fru-1-P (2), DHAP (3), glyceraldehyde (4), GAP (5)
fructokinase (FK), aldolase B (ALD-B), triosephosphate isomerase (TPI), triose kinase (TK)

Hereditary fructose intolerance is a rare enzyme defect that affects the breakdown of fructose in the liver. The aldolase B , which is normally the fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde splits, missing. Instead, only aldolase A is present, an enzyme of glycolysis whose substrate is fructose-1,6-bisphosphate and which cleaves fructose-1-phosphate at only one-fiftieth the speed of the enzyme.

The first enzyme in fructose breakdown , ketohexokinase , is not affected, so that the fructose gets into the liver cell, is phosphorylated and can no longer leave the cell. Due to the enzyme defect, the fructose-1-phosphate cannot be broken down, but accumulates and inhibits the enzymes involved in glycolysis (aldolase A), gluconeogenesis ( fructose-1,6-bisphosphatase ) and glycogen metabolism ( glycogen phosphorylase ). This can result in hypoglycemia, since when hungry the glycogen is no longer or only reduced to a reduced extent and no glucose can be formed from amino acids or glycerine.

genetics

HFI is caused by mutations in the aldolase B gene, which is on the long arm of chromosome 9. The mutations A149P, A174D and N334K are the most common defects in Europe and are responsible for around 85% of all patients with HFI. HFI is inherited in an autosomal recessive manner.

diagnosis

Clinical abnormalities only become apparent with the introduction of fructose in the diet, therefore only breastfed infants are completely symptom-free. Typical clinical features of the disease are vomiting, hypoglycaemia, coagulation disorders and shock. Evidence is provided by determining the enzyme defect in biopsy material from the liver, kidneys or small intestine or by means of a genetic test. This should definitely be carried out before a fructose stress test (i.e. the test for intestinal fructose intolerance ), as the latter can be life-threatening in the case of the very rare hereditary fructose intolerance (HFI): the enzyme deficiency in the liver with HFI would lead to ingested fructose is not broken down and would displace the glucose, the blood sugar, in the blood, whereupon the test subject could fall into a coma.

therapy

This disease cannot be treated with drugs. The complete elimination of fructose from food is therefore the only principle of therapy. In some cases, following the strict low-fructose diet improved HFI. During the first year of life, fruits and vegetables should be completely avoided and vitamins should be substituted. Chronic diet errors can sometimes manifest themselves in a growth disorder or in the development of rickets.

Earlier in the intensive care for parenteral nutrition infusions used FGX ( F ructose, G lucose and X ylit) are due to incompatibility in patients with fructose or Xylitintoleranz no longer used.

Control and forecast

Patients are monitored by determining blood coagulation parameters ( PTT , AT III ). These react very sensitively to even minor liver damage. The long-term prognosis is good; the only acute threats are intravenous fructose intake (for example from infusion therapy or parenteral nutrition).

See also

• Lactose intolerance
• Food intolerance

literature

• T. Schleip: Lactose and fructose intolerance: turmoil in the intestines. In: UGB forum. 1, 2004, pp. 9–11 ( online at: ugb.de ).
• A. Barth, N. Gaeta: At war with fruit sugar. In: UGB forum. 3, 2002, pp. 151–153 ( online at: ugb.de ).
• M. Sacherl: Hereditary fructose intolerance and fructose malabsorption - A handbook by those affected for those affected. Moers 2007, ISBN 978-3-00-021754-8 .
• Hans Konrad Biesalski among others: Nutritional medicine. 4th edition. Thieme Verlag, 2010, ISBN 978-3-13-100294-5 , pp. 817f.

Individual evidence

1. ^ Pschyrembel Clinical Dictionary 266th edition
2. ^ G. Löffler, PE Petrides, PC Heinrich: Biochemie & Pathobiochemie. 8th edition. Springer, Heidelberg 2006, ISBN 3-540-32680-4 , p. 395.
3. ↑ Gerald Huether: Tryptophan, serotonin, and melatonin: basic aspects and applications. In: Volume 467 of Advances in Experimental Medicine and Biology . 2nd Edition. Springer, 1999, ISBN 0-306-46204-4 , p. 74.
4. ↑ Hereditary fructose intolerance (HFI). In: Fachinformationen. IMD Institute for Medical Diagnostics Berlin-Potsdam GbR. At IMD-Berlin.de ( PDF ; 229 kB), accessed on October 6, 2019.

Web links

• Informative website about FM with many RECIPES and forum
• Self-help group for hereditary fructose intolerance (SHG-HFI)
• Table with foods containing fructose and their fructose / glucose content (PDF; 29 kB)

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !