What is Hereditary Fructose Intolerance (HFI)?
Hereditary Fructose Intolerance (HFI) is an inherited metabolic condition caused by a deficiency of the enzyme Aldolase B, which is normally found in the liver, kidneys and small intestine. Someone with HFI is born with it. Symptoms don’t generally appear until a baby is introduced to solid foods.
When does HFI present itself?
A person with HFI is affected from birth, meaning their dietary needs must be addressed right away. Symptoms often appear during bottle feeding if the formula contains fructose, or more frequently when solid foods like fruit, vegetables and other sugary foods are introduced to the child's diet.
What are the first symptoms of HFI?
Fructose, Sucrose and Sorbitol given to a child with HFI will result in a baby being very unsettled, frequently crying or screaming. It's often mistakenly attributed to "colic".
Diarrhoea, vomiting and gut pain are common symptoms. Ingestion of these sugars leads to low blood glucose levels, causing a baby to become pale and drowsy.
How is HFI acquired?
HFI is an inherited condition. It is a mutation of a recessive gene. This means that both parents will carry one mutation copy but will not have the condition themselves (unless one of them actually has HFI). If both parents are carriers, there is a 1 in 4 chance (25%) of giving birth to a child with HFI.
How often does it occur??
While global prevalence estimates suggest that HFI occurs in approximately 1 in 20,000 to 1 in 30,000 individuals, specific prevalence data for Australia is limited. Given the rarity of the condition, it's reasonable to infer that the prevalence in Australia aligns with global estimates.
As it is so rare, the diagnosis is often missed. It is vital that health professionals are made aware of the condition so they can consider this diagnosis when assessing a patient displaying symptoms.
What happens if HFI is not recognised or diagnosed?
Ingestion of Fructose, Sucrose or Sorbitol causes hypoglycaemia - abnormally low blood glucose levels. A child may be classed as 'Failure to Thrive'. Accumulated fructose acts as a toxin/poison and causes potential lasting damage to the liver, kidney and small intestine. If not recognised, this can result in death.
What happens in the body when fructose is ingested?
When someone with Hereditary Fructose Intolerance (HFI) ingests fructose, a metabolic traffic jam happens — and it can get serious quickly. Here's what goes on inside the body:
The Core Problem: Aldolase B Deficiency
In a healthy liver, fructose is broken down in a stepwise process:
- Fructose → Fructose-1-phosphate (by the enzyme fructokinase)
- Fructose-1-phosphate → split into usable sugars (glyceraldehyde + DHAP) by aldolase B
But in HFI, aldolase B is missing. So when fructose is consumed:
What Happens Next: Step-by-Step Breakdown
- Fructose gets trapped
- Fructose is still converted to fructose-1-phosphate (F1P) by fructokinase.
- But without aldolase B, F1P builds up in liver cells because it can’t be broken down.
- Phosphate gets stuck
- F1P ties up inorganic phosphate (Pi), depleting phosphate stores in the liver.
- Phosphate is crucial for making ATP, the cell’s energy currency.
- Energy crisis hits the liver
- With phosphate levels low, ATP production drops.
- The liver can’t perform basic functions like gluconeogenesis (making new glucose) or glycogenolysis (breaking down stored glycogen).
- Result? Severe hypoglycaemia (low blood sugar), especially after eating.
- Toxic effects kick in
- The accumulation of F1P and loss of energy:
- Damages liver cells
- Can lead to jaundice, vomiting, irritability, seizures, and even liver or kidney failure if exposure continues.
- The accumulation of F1P and loss of energy:
Why It’s Dangerous
Even small amounts of fructose, sucrose (which breaks down into fructose + glucose), or sorbitol (which gets converted to fructose) can trigger this cascade. It’s not just about discomfort — it’s a toxic reaction.
Quick Analogy
Think of it like a clogged sink:
- Water = fructose
- The drain = aldolase B
- Without the drain, water backs up fast — and floods the kitchen (aka damages your liver).
What happens if it's not recognised but the person survives?
Individuals with HFI develop a strong aversion to sweet tastes, which can be a lifesaving response. Continuing to consume unsafe sugars may cause liver and kidney damage. HFI may be detected by dentists when treating adults who have no dental decay, as the absence of cavities can be an indicator of the condition.
How is HFI treated?
There is no treatment as yet, but someone with HFI can stay healthy and well as long as they stick to a diet free of Fructose, Sucrose and Sorbitol. This diet is our lifesaver, but is often misunderstood, even by dieticians. The common and generalised concept of a "healthy" diet is poisonous for individuals with HFI.
Quick Summary:
| Cause | Genetic (enzyme deficiency) | Digestive issue (absorption problem) |
| Severity | Severe, potentially life-threatening | Generally mild to moderate |
| Onset | Infancy/early childhood | Any age |
| Affected Organ | Liver, Kidneys, Small Intestine (possible neurological affects - further research needed) | Gut (small intestine) |
| Diagnosis | Genetic test | Hydrogen breath test |
| Treatment | Complete avoidance of fructose/sucrose | Fructose-reduced diet |