Overview
Hyperinsulinism and hyperammonemia syndrome is characterized by persistent hyperammonemia and hypoketotic hypoglycemia, often linked to functional hyperactivity of hepatic glutamate dehydrogenase (GDH) 1.Diagnosis
Elevated blood ammonia levels (100-300 micromol/L) independent of protein intake 1.
Hypoketotic hypoglycemia, particularly postprandial 1.
Increased hepatic GDH activity (above normal range: 874 nmol/(min.mg protein)) with reduced GTP inhibition threshold 1.
Low plasma glutamine/blood ammonia ratio 1.Management
First-line treatment: Diazoxide for managing hyperinsulinism 1.
Adjunctive therapy: Oral N-carbamylglutamate to decrease blood ammonia levels 1.
Aggressive supportive measures: Dialysis or exchange transfusion in severe cases, particularly in neonates 2.Special Populations
Premature infants: Transient neonatal hyperammonemia (TNH) can occur and requires early aggressive treatment for favorable outcomes 2.Key Recommendations
Evaluate hepatic GDH activity and GTP inhibition sensitivity in patients with persistent hyperammonemia and hyperinsulinism for diagnosis 1 (Evidence: Moderate).
Initiate diazoxide therapy for managing hyperinsulinism in patients with hyperinsulinism/hyperammonemia syndrome 1 (Evidence: Moderate).
In neonates with suspected transient neonatal hyperammonemia, promptly institute dialysis or exchange transfusion to prevent neurological damage 2 (Evidence: Weak).References
1 Huijmans JG, Duran M, de Klerk JB, Rovers MJ, Scholte HR. Functional hyperactivity of hepatic glutamate dehydrogenase as a cause of the hyperinsulinism/hyperammonemia syndrome: effect of treatment. Pediatrics 2000. link
2 Rothberg AD, Thomson PD, Andronikou S, Cohen DF. Transient neonatal hyperammonaemia. A case report. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 1982. link