Abstract:

Objective To summarize the clinical features and genetic variation characteristics of children with fructose-1,6-bisphosphatase deficiency (FBP1D) caused by FBP1 gene variations. Methods Four pediatric patients with FBP1D admitted from January 2019 to June 2025 were enrolled as study subjects. Their clinical manifestations, laboratory findings, genetic testing results, treatment strategies, and prognosis were analyzed retrospectively. Additionally, a literature review was conducted to summarize data of previously reported Chinese FBP1D patients. Results The four patients were from four unrelated families, including 1 male and 3 females, with ages at diagnosis of 2 years and 3 months, 3 years and 5 months, 2 years and 11 months, and 4 years and 4 months, respectively. Core clinical presentations included fever, vomiting, anorexia, accompanied by drowsiness, fatigue, hyperhidrosis, and lethargy. Laboratory tests revealed hypoglycemia, metabolic acidosis, elevated lactate, and increased blood ketone bodies. All patients carried homozygous or compound heterozygous FBP1 gene variants, among which three novel variants were identified (c.242T>C, c.469G>C, c.115C>A). During a follow-up period of 6 months to 6 years, all patients achieved well-controlled disease under strict dietary management and close blood glucose monitoring, with essentially normal physical and mental development. As of December 20, 2025, a total of 38 FBP1D cases had been reported in China (23 males, 15 females), with the most common manifestations being hypoglycemia, metabolic acidosis, and convulsions. Approximately 81.6% of patients exhibited normal intellectual and motor development without neurological sequelae. The most frequent FBP1 gene variants were c.960dup, c.960del, c.490G>A, c.704del, and c.355G>A. Conclusion Ketotic hypoglycemia accompanied by metabolic acidosis and elevated lactate should raise suspicion of FBP1D, and genetic testing is recommended in such cases. Rational dietary management and blood glucose monitoring can effectively reduce the frequency of hypoglycemic episodes in FBP1D children. Hypoglycemic attacks tend to decrease with age, and most patients have a favorable prognosis.

Key words: ketotic hypoglycemia, FBP1 gene, fructose-1, 6-bisphosphatase deficiency, child