Endocrine Abstracts

Introduction: Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder causing failure of gluconeogenesis. Multiple mutations may produce the disease, of which 960/961insG is the commonest and is pan-ethnic. Hypoglycaemia, ketosis and lactic acidosis associated with the condition are triggered by infection, fasting or fructose/sucrose/sorbitol intake.

Aim: To present an atypical case of FBPase deficiency and to demonstrate findings of molecular analysis.

Case report: A 17-year-old Middle-Eastern female required three emergency hospital attendances within 1 year. Episodes occurred in the context of infection and consisted of decreased consciousness associated with hypoglycaemia (<0.2 mmol/l), metabolic acidosis (pH 6.9) with raised lactate (>10 mmol/l) and ketonuria. There was good recovery after each episode following administration of IV antibiotics, glucose, bicarbonate and fluids. Past medical history included diagnosis of beta-thalassaemia major since age 11 months and iron overload secondary to multiple blood transfusions causing hypogonadotrophic hypogonadism, short stature and liver siderosis. Supervised fasting excluded endogenous hyperinsulinaemia with appropriate insulin and C-peptide suppression. Further investigations revealed reduced leukocyte FBPase activity and absent liver FBPase activity. During childhood she experienced dizzy episodes – particularly if breakfast was missed, resolving with ingestion of honey. Contrary to what is expected, her episodes of metabolic derangement were relatively mild in infancy and only recently severe.

Methods: PCR of genomic DNA+sequencing.

Results and discussion: The 960/961insG mutation was identified – reported for the first time in a Middle-Eastern patient, confirming its pan-ethnicity. Acute management with early intravenous glucose and treatment of infection and specific dietary advice for the long term led to successful management of our patient. A disorder affecting the gluconeogenic pathway should be suspected in all patients developing unexplained severe acidosis and hypoglycaemia associated with infection.