Hereditary fructose intolerance (HFI) or fructose poisoning is a hereditary condition caused by a deficiency of liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s that metabolise

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 fructose

Fructose

Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

. It is also known as hereditary fructosemia.

Signs and symptoms

If fructose is ingested, other symptoms such as vomiting, hypoglycemia

Hypoglycemia

Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, jaundice

Jaundice

Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

, hemorrhage, hepatomegaly

Hepatomegaly

Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

, hyperuricemia

Hyperuricemia

Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...

 and eventually kidney failure will follow.

Cause

The deficient enzyme is aldolase-B, which converts fructose-1-phosphate

Fructose-1-phosphate

Fructose-1-phosphate is a derivative of fructose. It is generated by hepatic fructokinase.It is converted by aldolase B into glyceraldehyde and dihydroxyacetone phosphate ....

 to DHAP

Dhap

Dhap is a village development committee in Darchula District in the Mahakali Zone of western Nepal. At the time of the 1991 Nepal census it had a population of 4092 people living in 694 individual households.-External links:*...

 and glyceraldehyde

Glyceraldehyde

Glyceraldehyde is a triose monosaccharide with chemical formula C3H6O3. It is the simplest of all common aldoses. It is a sweet, colorless, crystalline solid that is an intermediate compound in carbohydrate metabolism...

. This means that the fructose cannot be further metabolised beyond fructose-1-phosphate. This traps phosphate

Phosphate

A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

s, which are needed to phosphorylate glycogen phosphorylase

Glycogen phosphorylase

Glycogen phosphorylase is one of the phosphorylase enzymes . Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond...

, which functions to release units of glucose-1-phosphate

Glucose-1-phosphate

Glucose 1-phosphate is a glucose molecule with a phosphate group on the 1'-carbon.-Catabolic:In glycogenolysis, it is the direct product of the reaction in which glycogen phosphorylase cleaves off a molecule of glucose from a greater glycogen structure.To be utilized in cellular catabolism it must...

 from glycogen. (Glucose-1-phosphate is converted to glucose-6-phosphate

Glucose-6-phosphate

Glucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cells as the vast majority of glucose entering a cell will become phosphorylated in this way....

 and then dephosphorylated to form glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

).

In addition, Aldolase A plays an important role in gluconeogenesis

Gluconeogenesis

Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

, producing fructose-1,6-bisphosphate from glyceraldehyde-3-phosphate and DHAP. Though glucose may still be released through the breakdown of glycogen

Glycogen

Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

, it cannot be synthesized from gluconeogenesis

Gluconeogenesis

Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

. This causes severe hypoglycemia

Hypoglycemia

Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

.

Common Traits

• Refusal to eat or dislike of many fruits, vegetables, candies, and baked goods.
• Love of dextrose-based candies.
• Primary beverages are milk, water, unsweetened tea, and unsweetened coffee.
• Feeling nauseated, sick, queasy, shaky, and/or foggy shortly after consuming fructose or sucrose.
• Kidney pain, hypoglycemia, and weakness ensuing a few hours to a couple days after consuming fructose or sucrose.
• Tendency to binge eat on "safe" foods after consuming fructose. Safe foods can include dairy, potato chips, pasta and rice.

Treatment

Treatment is with a fructose free diet, which if adhered to, is concordant with a good prognosis.

Fructose and sucrose eliminated from diet.

Related conditions

Hereditary fructose intolerance should not be confused with fructose malabsorption

Fructose malabsorption

Fructose malabsorption, formerly named "dietary fructose intolerance," is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers in the small intestine's enterocytes. This results in an increased concentration of fructose in the entire intestine.Fructose...

. The latter was formerly known as dietary fructose intolerance (DFI), a deficiency of fructose transporter protein in the enterocyte

Enterocyte

Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...

s, which leads to abdominal bloating

Bloating

Bloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Symptoms:The most common...

, diarrhea

Diarrhea

Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

 and/or constipation

Constipation

Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

.

External links

• Boston University HFI Lab
• http://www.uihealthcare.com/topics/medicaldepartments/foodandnutrition/dfi/whatisdfi.html
• Food-Info.net Fructose Intolerance (with list of acceptable and non-acceptable carbohydrates)
• http://www.bu.edu/aldolase/HFI/hfiinfo/detail.html
• Case Study
• HFI-Info Discussion Board