ALDOB gene
Also known as: Fructosemia
OMIM # 229600 https://omim.org/entry/229600
1. The Disease:
Hereditary fructose intolerance (HFI) is an autosomal recessive disorder of fructose (a type of monosaccharide sugar) metabolism, resulting from a deficiency of hepatic fructose-1-phosphate aldolase activity and leading to gastrointestinal disorders and postprandial hypoglycemia following fructose ingestion. HFI is a benign condition when treated, but it is life threatening and potentially fatal if left untreated. HFI is inherited in an autosomal recessive pattern – a mutation must be present in the copies inherited from both the mother and the father – for the disease to manifest itself.
2. The Symptoms:
HFI usually presents in infancy at the time of weaning (when fructose is added to the diet), manifesting with hypoglycemia, lactic acidosis, ketosis with recurrent vomiting, abdominal pain and systemic manifestations following consumption of fructose-containing foods.
Persistent ingestion of fructose and related sugars (such as sucrose and sorbitol) may lead to growth retardation, hepatomegaly, proximal tubular dysfunction, liver and renal failure, seizures, coma and risk of death.
All patients achieve adulthood, develop a natural aversion to fruit/sweets and report a life long history of vomiting and hypoglycemia following fructose ingestion.
3. Actions to take in case of early diagnosis:
- Infants with a positive genetic test (having 2 mutations or 2 copies of a single mutations in the ALDOB gene) should continue breastfeeding and be aware/ avoid milk formula containing fructose, sucrose and sorbitol. Early treatment, through diet restriction of fructose can solve all symptoms.
- Infants with a positive genetic test should have confirmatory HFI testing through one of the following methods:
- When clinical features, nutritional and family history are suggestive. Very rarely, liver biopsy may be performed to assess aldolase B activity.
- A combination of parental genetic testing to access segregation of the two mutations (expecting them to be in trans) and clinical trial with fructose restriction diet may be indicated, especially infants still without symptoms.
- HFI is a lifelong disease that requires lifetime compliance to dietary management. Regular follow-up with a metabolic disease specialist and a multidisciplinary approach to care, including pediatrics, genetics and dietician.
- HFI prognosis is favorable with normal growth, intelligence and lifespan if treated with good compliance to a low-fructose, sucrose and sorbitol diet divided in balanced meals.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
- Management of acute crises: Acute crises are more frequent in early life – neonatal period, infancy, and early childhood – with gradual decrease afterwards.
- Intervention (oral glucose or IV dextrose) should take place early in an acute crisis while the blood glucose is normal due to the possibility of delayed hypoglycemia, which only occurs relatively late in the course of acute metabolic decompensation. Acute management guidelines are available from the British Inherited Metabolic Disease Group. See link for the protocol: https://bimdg.org.uk/store/guidelines/ER-f16bisP-v4_567327_09092016.pdf
4. For more information
Biblio: https://www.ncbi.nlm.nih.gov/books/NBK333439/