Hereditary fructose intolerance: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
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. | 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. | ||
==Causes== | ==Causes== | ||
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 [[phosphate]]s; 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]]). | 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 [[phosphate]]s; 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]]). | ||
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==Differentiating {{PAGENAME}} from Other Diseases== | ==Differentiating {{PAGENAME}} from Other Diseases== | ||
Hereditary Fructose Intolerance must be differentiated from other diseases that cause [ | 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== | ==Epidemiology and Demographics== | ||
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==Risk Factors== | ==Risk Factors== | ||
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===History and Symptoms=== | ===History and Symptoms=== | ||
If fructose is ingested, other symptoms such as vomiting, [[hypoglycemia]], [[jaundice]], [[hemorrhage]], [[hepatomegaly]], [[hyperuricemia]] and eventually [[kidney failure]] will follow. | |||
===Physical Examination=== | ===Physical Examination=== | ||
Revision as of 03:32, 15 July 2021
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Hereditary fructose intolerance (HFI) or fructose poisoning is a hereditary condition caused by a deficiency of liver enzymes that metabolise fructose.
Historical Perspective
Classification
Pathophysiology
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.
Causes
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
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
- 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.
Diagnosis
Diagnostic Criteria
History and Symptoms
If fructose is ingested, other symptoms such as vomiting, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and eventually kidney failure will follow.
Physical Examination
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
Treatment is with a fructose free diet, which if adhered to, is concordant with a good prognosis. [1]
Fructose and sucrose eliminated from diet. [2]
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Related conditions
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.
See also
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)
- [2]
- HFI-Info Discussion Board