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Fructose-1,6-biphosphatase (FBP) deficiency is a disorder of fructose metabolism (see this term) characterized by recurrent episodes of fasting hypoglycemia with lactic acidosis, that may be life-threatening in neonates and infants.
ORPHA:348Classification level: Disorder
FBP deficiency birth prevalence has been estimated at 1/147,575 in Italy. This disorder has been reported in Japanese, Asian, European, North American, Arab and Moroccan patients.
FBP deficiency may occur neonatally with hepatomegaly, but it usually presents in infants of 3-4 months of age or early childhood, with manifestations including fast-induced hypoglycemia and metabolic acidosis, episodes of tachypnea/apnea, hypoglycemia, ketosis and lactic acidosis. Episodes are often triggered by catabolic conditions such as prolonged fasting (more than 8 to 10 hours), fructose, sorbitol or glycerol ingestion, vomiting, diarrhea or febrile infectious diseases. Patients are asymptomatic between episodes.
FBP deficiency is due to homozygous or compound heterozygous mutations in the FBP1(9q22) gene encoding fructose-1,6-bisphosphatase1, resulting in impaired gluconeogenesis. To date, 11deleterious mutations have been reported.
FBP deficiency diagnosis is based on clinical presentation, along with glycemia and lactacidemia levels. Enzyme activity may be measured in leukocytes, and genetic testing of the FBP1 gene confirms diagnosis.
Differential diagnosis includes glycogen storage disease due to glucose-6-phosphatase deficiency (see this term).
Prenatal diagnosis is feasible through molecular analysis of amniocytes or chorionic villous cells.
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
FBP deficiency management aims at avoiding hypoglycemia and lactic acidosis through frequent feeding, enriched with glucose or maltodextrin, especially in illness associated with fever. Prevention and treatment of metabolic decompensation (with glucose orally or intravenously) is essential. Fasting periods longer than 8 hours should be avoided and infectious episodes should be carefully monitored. Fructose or sucrose should be avoided during acute episodes.
With timely adapted management and proper treatment, FPB deficiency prognosis is excellent, even if this condition may be potentially fatal in the newborn period and early infancy.