National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Hereditary fructose intolerance


Other Names:
Fructose-1-phosphate aldolase deficiency; ALDOB deficiency; Aldolase B deficiency; Fructose-1-phosphate aldolase deficiency; ALDOB deficiency; Aldolase B deficiency; Fructose-1,6-bisphosphate aldolase B deficiency; Fructose intolerance, hereditary See More
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Hereditary fructose intolerance (HFI) is a metabolic disease caused by the absence of an enzyme called aldolase B. In people with HFI, ingestion of fructose (fruit sugar) and sucrose (cane or beet sugar, table sugar) causes severe hypoglycemia (low blood sugar) and the build up of dangerous substances in the liver. HFI may be relatively mild or a very severe disease.[1] The condition is caused by mutations in the ALDOB gene. It is inherited in an autosomal recessive pattern.[2] Treatment involves eliminating fructose and sucrose from the diet. In the severe form, eliminating these sugars from the diet may not prevent progressive liver disease.[1]
Last updated: 8/20/2015

The symptoms of HFI include:[1]

  • Poor feeding as a baby
  • Irritability
  • Increased or prolonged neonatal jaundice
  • Vomiting
  • Convulsions
  • Excessive sleepiness
  • Intolerance for fruits
  • Avoidance of fruits and fructose/sucrose-containing foods
  • Doing well after eating foods without fructose/sucrose

The early symptoms of fructose intolerance may resemble those of galactosemia: irritability, jaundice, vomiting, convulsions and an enlarged liver and spleen. Later problems relate more to liver disease.[1]

Last updated: 8/20/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 42 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain
[ more ] 		0002027
Reduced aldolase level 0012545
30%-79% of people have these symptoms
Diarrhea
Watery stool
0002014
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ] 		0001510
Nausea 0002018
5%-29% of people have these symptoms
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating
[ more ] 		0003270
Abnormality of the coagulation cascade 0003256
Chronic hepatic failure
Chronic liver failure
0100626
Chronic kidney disease 0012622
Constipation 0002019
Episodic hyperhidrosis
Sporadic excessive sweating
0001069
Hepatomegaly
Enlarged liver
0002240
Hypermagnesemia
High blood magnesium levels
0002918
Hyperuricemia
High blood uric acid level
0002149
Hypophosphatemia
Low blood phosphate level
0002148
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
Metabolic acidosis 0001942
Reactive hypoglycemia
Low blood sugar after a meal
0012051
Vomiting
Throwing up
0002013
1%-4% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Coma 0001259
Lethargy 0001254
Seizure 0001250
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Bicarbonaturia 0003646
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Elevated hepatic transaminase
High liver enzymes
0002910
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Fructose intolerance 0005973
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Glycosuria
Glucose in urine
0003076
Hepatic steatosis
Fatty infiltration of liver
Fatty liver
[ more ] 		0001397
Hyperbilirubinemia
High blood bilirubin levels
0002904
Hyperphosphaturia
High urine phosphate levels
0003109
Hyperuricosuria
High urine uric acid level
0003149
Hypoglycemia
Low blood sugar
0001943
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Lactic acidosis
Increased lactate in body
0003128
Malnutrition 0004395
Proximal renal tubular acidosis 0002049
Proximal tubulopathy 0000114
Transient aminoaciduria 0008273
Showing of 42 |
Last updated: 7/1/2020
HFI is caused by alterations (mutations) in the ALDOB gene.[2] This gene provides instructions for making an enzyme called aldolase B. This enzyme is primarily found in the liver and is involved in the breakdown of fructose into energy. Mutations in the ALDOB gene reduce the function of the enzyme, impairing its ability to metabolize fructose. This causes a toxic buildup of fructose-1-phosphate in liver cells, which results in the death of liver cells over time.[2] 
Last updated: 8/20/2015
HFI is inherited in an autosomal recessive manner, which means alterations (mutations) are present in both copies of the ALDOB gene.[1][2] The parents of an individual with HFI each carry one copy of the mutated gene, but they typicaly do not show signs and symptoms of the condition.[2] 
Last updated: 8/21/2015

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

Complete elimination of fructose and sucrose from the diet is an effective treatment for most people,[1] although this can be challenging. More information on treatment for HFI is available from the HFI Laboratory at Boston University at the following link. This page includes information on what people with HFI can and cannot eat.
http://www.bu.edu/aldolase/HFI/treatment/

Additional information on foods to avoid if you have HFI is available from the Mayo clinic.
http://www.mayoclinic.com/health/fructose-intolerance/AN01574
Last updated: 8/21/2015

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include pyloric stenosis, gastro-esophageal reflux,galactosemia, tyrosinemia, glycogen storage disease, ornithine transcarbamoylase deficiency, Wilson disease, tumor of hematopoietic and lymphoid tissue (see these terms) and fructose malabsorption.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Hereditary fructose intolerance. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • More information on research for hereditary fructose intolerance is available from the HFI Laboratory at Boston University.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Hereditary fructose intolerance. This website is maintained by the National Library of Medicine.
  • The Mayo Clinic provides additional information on foods to avoid if you have hereditary fructose intolerance.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary fructose intolerance. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Haldeman-Englert C. Hereditary fructose intolerance. Medline Plus. May 2, 2013; http://www.nlm.nih.gov/medlineplus/ency/article/000359.htm. Accessed 8/20/2015.
  2. Hereditary fructose intolerance. Genetics Home Reference. June 2011; http://ghr.nlm.nih.gov/condition/hereditary-fructose-intolerance. Accessed 8/20/2015.