The First Reported Albanian Patient With Fructose-1,6-Bisphosphatase Deficiency: A Rare Disorder of Fructose Metabolism.

Abstract

Background: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare autosomal recessive disorder of gluconeogenesis caused by biallelic pathogenic variants in the FBP1 gene. It presents with episodic hypoglycemia, lactic acidosis, and ketone body abnormalities, particularly during catabolic stress, but often mimics more common metabolic disorders, leading to diagnostic delays. Case Presentation: We describe the first genetically confirmed Albanian case of FBPase deficiency in a 3-year-old girl, born to nonsanguineous parents. The patient presented with recurrent episodes of vomiting, hypoglycemia, and metabolic decompensation since infancy. At her most severe presentation, she was admitted in a subcomatose state with profound hypoglycemia (35 mg/dL) and lactic acidosis (pH 6.9) without ketonuria. Whole exome sequencing identified a homozygous pathogenic FBP1 variant NM_000507.3(FBP1): c.472C > T; p. (Arg158Trp), a recurrent missense mutation associated with significant phenotypic variability. Parental testing confirmed autosomal recessive inheritance. Management and Outcome: Emergency management included intravenous dextrose and bicarbonate for metabolic acidosis, followed by nutritional interventions. The patient was advised to avoid fasting for more than 8 h and to limit fructose intake. No further metabolic crises were observed after these interventions. Conclusion: This case highlights the clinical and genetic complexity of FBPase deficiency and underlines the importance of genomic diagnostics in children with unexplained hypoglycemia and metabolic acidosis. Early diagnosis allows effective dietary management and prevents recurrent life-threatening episodes. As the first reported case in Albania, it contributes to the growing recognition of FBPase deficiency as an underdiagnosed but treatable metabolic disorder.