A girl with intractable absence seizures and facial myoclonia at age 7 years was eventually diagnosed with hyperinsulinism-hyperammonemia syndrome because of hypoglycemia, hyperinsulinism, hyperammonemia, and the results of an oral L-leucine loading test. Her seizures occurred even during periods of relatively normal blood glucose levels, and were completely suppressed by diazoxide treatment only. Her diagnosis of hyperinsulinism-hyperammonemia syndrome was confirmed by a loss of sensitivity of glutamate dehydrogenase for guanosine 5'-triphosphate. Genetic studies identified the I444M mutation in the GLUD1 gene, which encodes glutamate dehydrogenase. This case illustrates the complex relationship between seizures and hypoglycemia in hyperinsulinism-hyperammonemia syndrome that can create diagnostic difficulties. The possibility of hyperinsulinism-hyperammonemia syndrome should be considered in patients with refractory absence seizures with myoclonia. (C) 2012 Elsevier Inc. All rights reserved.