Hereditary fructose intolerance
Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief:
Hereditary fructose intolerance (HFI) or fructose poisoning is a hereditary condition caused by a deficiency of liver enzymes that metabolise fructose.
HFI is an autosomal recessive condition caused by mutations in the ALDOB gene, located at 9q31.1, causing deficiency of the enzyme aldolase B. Fructose-1-phosphate is metabolized by aldolase B into dihydroxyacetone phosphate and glyceraldehyde. A deficiency of aldolase B results in an accumulation of fructose-1-phosphate, and trapping of phosphate (fructokinase requires adenosine triphosphate (ATP)). The downstream effects of this enzyme block are the inhibition of glucose production and reduced regeneration of ATP. Individuals affected with HFI are asymptomatic until they ingest fructose, sucrose, or sorbitol. If fructose is ingested, the enzymatic block at aldolase B causes an accumulation of fructose-1-phosphate which, over time, results in the death of liver cells.
Hereditary Fructose Intolerance is inherited in an autosomal recessive pattern. The parents of the patients are carriers as they have one copy of mutated gene and they do not usually shows symptoms or signs.The deficient enzyme is aldolase-B, which converts fructose-1-phosphate to DHAP and glyceraldehyde. This means that the fructose cannot be further metabolised beyond fructose-1-phosphate. This traps phosphates; which are needed to phosphorylate glycogen phosphorylase which carries on to release units of glucose-1-phosphate from glycogen. (Glucose-1-phosphate gets converted to glucose-6-phosphate and then dephosphorylated to form glucose).
In addition, aldolase-B plays an important role in gluconeogenesis, producing fructose-1,6-bisphosphate from glyceraldehyde-3-phosphate and DHAP. Thus, glucose cannot be released through the breakdown of glycogen nor can it be synthesized from gluconeogenesis, resulting in severe hypoglycemia. Hereditary fructose intolerance is inherited. If both parents are carriers for aldolase B gene, each of their children has a 25% (1 in 4) chance of being affected.
Differentiating Hereditary fructose intolerance from Other Diseases
Hereditary Fructose Intolerance must be differentiated from other diseases that cause diarrhea and abdominal pain such as Fructose malabsorption, formerly named dietary fructose intolerance (DFI).
Epidemiology and demographics
The incidence of hereditary fructose intolerance is approximately 1 in 20,000 to 30,000 individuals each year worldwide.
Natural History, Complications, and Prognosis
- Early symptoms are similar to those of galactosemia (inability to use the sugar galactose). Later symptoms relate more to liver disease. Symptoms may include: convulsions, excessive sleepiness, Irritability, jaundice, poor feeding and growth, failure to thrive, vomiting.
- The symptoms of hereditary fructose intolerance typically develop when the baby starts eating fruits and other foods that contain fructose or sucrose.
- In HFI, the diagnosis of homozygotes is difficult, requiring a genomic DNA screening with allele specific probes or an enzyme assay from a liver biopsy.
- Individuals who suspect they might have HFI, should avoid testing via fructose challenge as the results are non-conclusive for individuals with HFI and even if the diagnostic administration fructose is properly controlled, profound hypoglycemia and its sequelae can threaten the patient's well-being.
History and Symptoms
If fructose is ingested, other symptoms such as vomiting, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and eventually kidney failure will follow.
HFI clinical manifestations can be preventable, as it responds to dietary therapy.
Other Diagnostic Studies
- The mainstay of treatment is with a fructose free diet, which if adhered to, is concordant with a good prognosis. 
- Stable patients without acute intoxication events are treated by careful dietary planning that avoids fructose and its metabolic precursors. Fructose is replaced in the diet by glucose, maltose or other sugars. Management of patients with HFI often involves dietitians who have a thorough knowledge of what foods are acceptable.
Hereditary fructose intolerance should not be confused with fructose malabsorption. The latter is the same as dietary fructose intolerance (DFI), a deficiency of fructose transporter enzyme in the enterocytes, which leads to abdominal bloating, diarrhea and/or constipation.
- Boston University HFI Lab
- Food-Info.net Fructose Intolerance (with list of acceptable and non-acceptable carbohydrates)
- HFI-Info Discussion Board
- ↑ Ali M, Rellos P, Cox TM (1998). "Hereditary fructose intolerance". J Med Genet. 35 (5): 353–65. doi:10.1136/jmg.35.5.353. PMC 1051308. PMID 9610797.
- ↑ Template:GPnotebook
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