Rare Immunology News

Disease Profile

Hereditary fructose intolerance

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

All ages

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ICD-10

E74.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Fructose-1-phosphate aldolase deficiency; ALDOB deficiency; Aldolase B deficiency;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Kidney and Urinary Diseases;

Summary

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]?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

Symptoms

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]

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.

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

Cause

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]

Diagnosis

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

    Treatment

    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.
    https://www.bu.edu/aldolase/HFI/treatment/

    Additional information on foods to avoid if you have HFI is available from the Mayo clinic.
    https://www.mayoclinic.com/health/fructose-intolerance/AN01574

    Organizations

    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

      Learn more

      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

      • 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.
      • Genetics Home Reference (GHR) contains information on Hereditary fructose intolerance. This website is maintained by the National Library of Medicine.
      • 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.

          References

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

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