Hereditary fructose intolerance

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may not grow and gain weight at the expected rate (faltering weight).

Repeated ingestion of fructose-containing foods can lead to liver and kidney damage. The liver damage can result in a yellowing of the skin and whites of the eyes (jaundice), an enlarged liver (hepatomegaly), and chronic liver disease (cirrhosis). Continued exposure to fructose may result in seizures, coma, and ultimately death from liver and kidney failure. Due to the severity of symptoms experienced when fructose is ingested, most people with hereditary fructose intolerance develop a dislike for fruits, juices, and other foods containing fructose.

Hereditary fructose intolerance should not be confused with a condition called fructose malabsorption. In people with fructose malabsorption, the cells of the intestine cannot absorb fructose normally, leading to bloating, diarrhea or constipation, flatulence, and stomach pain. Fructose malabsorption is thought to affect approximately 40 percent of individuals in the Western hemisphere; its cause is unknown.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ALDOB gene cause hereditary fructose intolerance. The ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is found primarily in the liver and is involved in the breakdown (metabolism) of fructose so this sugar can be used as energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into other molecules called glyceraldehyde and dihydroxyacetone phosphate.

ALDOB gene mutations reduce the function of the enzyme, impairing its ability to metabolize fructose. A lack of functional aldolase B results in an accumulation of fructose-1-phosphate in liver cells. This buildup is toxic, resulting in the death of liver cells over time. Additionally, the breakdown products of fructose-1-phosphase are needed in the body to produce energy and to maintain blood sugar levels. The combination of decreased cellular energy, low blood sugar, and liver cell death leads to the features of hereditary fructose intolerance.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of hereditary fructose intolerance is estimated to be 1 in 20,000 to 30,000 individuals each year worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abdominal pain · Very frequent (99-80%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.

Reduced aldolase level · Very frequent (99-80%)

Concentration of fructose 1,6-bisphosphate aldolase in the blood circulation below the lower limit of normal.

Diarrhea · Frequent (79-30%)

Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.

Growth delay · Frequent (79-30%)

A deficiency or slowing down of growth pre- and postnatally.

Nausea · Frequent (79-30%)

A sensation of unease in the stomach together with an urge to vomit.

Abdominal distention · Occasional (29-5%)

Distention of the abdomen.

Abnormality of the coagulation cascade · Occasional (29-5%)

An abnormality of the coagulation cascade, which is comprised of the contact activation pathway (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway) as well as cofactors and regulators.

Chronic kidney disease · Occasional (29-5%)

Functional anomaly of the kidney persisting for at least three months.

Other findings in the same source

From: Orphanet

Additional reported features include Constipation (Occasional (29-5%)); Episodic hyperhidrosis (Occasional (29-5%)); Hepatomegaly (Occasional (29-5%)); Hypermagnesemia (Occasional (29-5%)); Hyperuricemia (Occasional (29-5%)); Hypophosphatemia (Occasional (29-5%)); Jaundice (Occasional (29-5%)); Metabolic acidosis (Occasional (29-5%)); Reactive hypoglycemia (Occasional (29-5%)); Renal insufficiency (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Hereditary fructose intolerance is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hereditary fructose intolerance. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.