General description

Fructose-1,6-bisphosphatase deficiency (FBP1D) is a rare autosomal recessive disorder caused by mutations in the FBP1 gene, leading to impaired gluconeogenesis and metabolic crises. FBP1D results from deficient activity of fructose-1,6-bisphosphatase (FBPase), a rate-limiting enzyme in gluconeogenesis that converts fructose-1,6-bisphosphate to fructose-6-phosphate. This defect disrupts glucose production from precursors like lactate, glycerol, and amino acids, causing hypoglycemia during fasting.

Acute crises typically present in infancy or early childhood with:

• Hypoglycemia (often severe, triggered by fasting or fever)
• Lactic acidosis and ketosis, manifesting as tachypnea, apnea, or hyperventilation
• Neurological complications: seizures, reduced consciousness, or coma
• Hepatic involvement: hepatomegaly, elevated transaminases, and steatosis

Chronic sequelae include intellectual disability in cases of delayed diagnosis due to recurrent hypoglycemic brain injury. Long-term outcomes are favorable with early dietary management avoiding prolonged fasting and limiting fructose intake.

References

1. Mei, Shiyue, et al. "Status epilepticus due to fructose-1, 6-bisphosphatase deficiency caused by FBP1 gene mutation." Pediatric Investigation 3.02 (2019): 122-126.