Background: Congenital hyperinsulinism (CHI) is the most frequent cause of recurrent episodes of hypoglycemia in infancy and results from different underlying genetic defects. The hyperinsulinism-hyperammonemia syndrome (HHS) has been shown to result from dominant germ line mutations within the glutamate dehydrogenase gene (GLUD1, OMIM *138130). Diagnosis of this entity is of clinical importance since invasive diagnostic procedures which are performed to identify focal pancreatic lesions are not necessary in HHS. Therefore, we investigated whether urinary concentration of alpha-ketoglutarate (alpha-KG) is elevated in patients with hyperinsulinism. Methods: Excretion of alpha-KG was measured by gas-chromatography/mass spectrometry (GC/MS) in eight patients with an activating GLUD1 mutation and 90 controls. Results: Urinary alpha-KG was significantly elevated in seven of eight patients when compared to controls. Hyperammonemia was found in six of the eight patients with HHS. No relation was found between the underlying GLUD1 mutation and the level of urinary alpha-KG as well as the presence or absence of hyperammonemia. Conclusion: Urinary alpha-KG is elevated in most patients with HHS and should be included in the work-up of patients with hyperinsulinism.
