FBP1 gene
Also known as: FBP1 Deficiency; FBPase Deficiency; Fructose 1,6 Diphosphatase Deficiency
OMIM # 229700 https://omim.org/entry/229700
1. The Disease:
Fructose-1,6-bisphosphatase deficiency (FBP1D) is characterized by episodic acute crises of lactic acidosis and ketotic hypoglycemia, manifesting as hyperventilation, apneic spells, seizures, and/or coma.
2. The Symptoms:
Acute crises are most common in early childhood; nearly half of affected children have hypoglycemia in the neonatal period (especially the first 4 days) resulting from deficient glycogen stores. Factors known to trigger episodes include fever, fasting, decreased oral intake, vomiting, infections, and ingestion of large amounts of fructose. In untreated individuals, symptoms worsen progressively as continued catabolism leads to multiorgan failure (especially liver, brain, and later heart). Morbidity and mortality are high. Sepsis, blindness, and Reye syndrome-like presentation have been reported. In between acute episodes, children are asymptomatic.
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 gene FBP1) should continue breastfeeding and be aware/ avoid milk formula containing fructose, sucrose and sorbitol. Early treatment, through diet restriction of fructose is indicated.
- Infants with a positive genetic test should have confirmatory 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 fructose-1,6-bisphosphatase 1 (FBP1) activity or it can be made in mononuclear white blood cells (not widely available).
- 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 in infants still without symptoms.
- FBP1D 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.
- FBP1 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.
- Just, a few have intellectual disability, presumably due to early and prolonged hypoglycemia.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.