Fructose-1,6-bisphosphatase deficiency initially diagnosed as acute necrotizing encephalopathy in a child: a case report

Fructose-1,6-bisphosphatase (FBP1) deficiency is a rare inherited defect of gluconeogenesis that can cause fasting- or infection-triggered hypoglycemia, lactic acidosis, and multisystem biochemical disturbances. Acute metabolic crises may produce symmetric deep gray-matter or diffuse cortical abnormalities on neuroimaging, mimicking infection-triggered encephalopathy syndromes such as acute necrotizing encephalopathy (ANE). We report a school-aged patient whose presentation and early imaging suggested ANE but was ultimately explained by genetically confirmed fructose-1,6-bisphosphatase deficiency. A previously healthy 7-year-old girl was found in a coma with ongoing generalized seizures and fever. Her fingerstick glucose was 1.8 mmol/L. Clinical tests showed metabolic acidosis (pH 7.22), significant hyperlactatemia, hyperuricemia, low sodium levels, and high transaminases and lactate dehydrogenase. Initial brain magnetic resonance imaging (MRI) showed mild bilateral thalamic hyperintensity, with high levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in the cerebrospinal fluid, prompting empiric treatment with high-dose corticosteroids, intravenous immunoglobulin, intrathecal corticosteroids, tocilizumab and intensive supportive care. The patient improved after metabolic correction. A follow-up MRI on day 7 revealed extensive bilateral hemispheric abnormalities atypical for necrotizing encephalopathy. Infectious causes were ruled out. Whole-exome sequencing identified a homozygous c.490G > A (p.Gly164Ser) mutation in the FBP1 gene; both parents were heterozygous, and a sibling was also homozygous. Treatment focused on prompt glucose administration, correcting acidosis, and dietary management. The patient was discharged on day 22 in stable condition, with complete resolution of acute abnormal signals, and remained asymptomatic at six months. Fructose-1,6-bisphosphatase deficiency can present beyond infancy and mimic necrotizing encephalopathy. Recognition of severe hypoglycemia, lactic acidosis, and multisystem abnormalities should prompt immediate metabolic stabilization and targeted genetic testing to avoid misdiagnosis and unnecessary immunomodulatory therapy.