IllnessFructose-1,6-biphosphatase deficiency, differential diagnosis

NGS +

Fructose-1,6-bisphosphatase (FBP1) deficiency is characterised by recurrent acute crises with lactic acidosis and ketotic hypoglycaemia, clinically manifesting as hyperventilation, respiratory arrest, seizures and/or coma. Acute crises occur most frequently in early childhood; almost half of affected children suffer hypoglycaemia as newborns (especially in the first four days of life), as they do not yet have glycogen stores to fall back on. Factors that can trigger crises include fever, fasting and reduced food intake, vomiting, infections and the intake of large amounts of fructose (particularly contained in pome fruit, berries, exotic fruits (e.g. persimmons) and honey as well as part of household sugar).

Without treatment, the symptoms gradually worsen as the persistent catabolic metabolism leads to multi-organ failure (especially liver, brain and later heart).

Between acute episodes, children are asymptomatic. While the majority of affected children show normal growth and psychomotor development, a few have mental retardation, probably due to early prolonged hypoglycaemia.

The suspected diagnosis is confirmed by the detection of pathogenic FBP1 variants. FBP1 deficiency follows an autosomal recessive mode of inheritance. Hereditary fructose intolerance (HFI), beta-kethothiolase deficiency, glycogen storage disease type 1, pyruvate carboxylase deficiency, PGM1-CDG and fructose malabsorption or other disorders of glucose/fructose and fat metabolism and disorders of the mitochondrial respiratory chain or the citrate cycle should be considered in the differential diagnosis.

The clinical diagnosis of FBP deficiency is made on the basis of the symptoms and the glycaemia and lactazide levels. Unremarkable molecular genetic findings do not rule out the clinical diagnosis.

(https://www.ncbi.nlm.nih.gov/books/NBK550349/)

• Alias: Fructose-1,6-diphosphatase deficiency (FBP1)
• Alpha-methylacetoacetic aciduria (ACAT1)
• Congenital disorder of glycosylation, type It (PGM1)
• Fructose intolerance, hereditary (ALDOB)
• Glycogen storage disease Ia (G6PC1)
• Glycogen storage disease Ib + Ic (SLC37A4)
• Pyruvate carboxylase deficiency (PC)