Clinical and molecular characterization of 14 Egyptian children with fructose-1,6-bisphosphatase deficiency.

backgroundFructose-1,6-bisphosphatase (FBP1) deficiency is a rare inherited disease characterized by recurrent episodes of lactic acidosis and ketotic hypoglycemia. To date, no cases have been reported in the Egyptian population. This study aimed to elucidate the phenotypic and molecular spectrum of FBP1 deficiency in Egypt.

methodsThis observational study included children with FBP1 deficiency diagnosed and managed at an Egyptian medical center between 2022 and 2024. Clinical and laboratory data of acute metabolic episodes were thoroughly reviewed. All patients underwent blood acylcarnitine assay, urinary organic acids analysis, and whole-exome sequencing. Patients' outcomes were classified into favorable, neurodevelopmental impairment, and death.

resultsThis cohort included 14 Egyptian children (from 11 families) with FBP1 deficiency. The median age at disease onset was 13 months, ranging from the first week of life to 36 months. All patients exhibited acute lactic acidosis, and most (13/14) had hypoglycemia. Four FBP1 variants were identified: c.88G > T (p.Glu30Ter), c.652_661delinsTCACGAGGGCT (p.Arg218SerfsTer9), c.960delinsGG (p.Ser321ValfsTer13), and c.902_904del (Glu301del). The c.960delinsGG variant was detected in nine cases, suggesting a founder effect. The c.652_661delinsTCACGAGGGCT is a novel variant. One case had a coexisting partial biotinidase deficiency. Regarding outcome, two patients died during the neonatal period, while the remainder achieved normal neurodevelopment.

conclusionThis is the first study of FBP1 deficiency in Egypt, which expands the demographic, clinical, and genetic spectrum of this rare disease.