A SYNDROME OF CONGENITAL HYPERINSULINISM AND HYPERAMMONEMIA

This report describes two patients from unrelated families with an unu sual syndrome of hyperinsulinism plus hyperammonemia. The diagnosis of hyperinsulinism was based on the demonstration of fasting hypoglycemi a with inappropriately elevated insulin levels, inappropriately low-be ta-hydroxybutyrate and free fatty acid levels, and inappropriately lar ge glycemic response to the administration of glucagon. In both patien ts, plasma ammonium levels were persistently elevated and unaffected b y protein feeding, protein restriction, or benzoate therapy. Plasma an d urinary amino acids, urinary organic acids, and urinary erotic acid levels were not consistent with any of the urea cycle enzyme defects o r other hyperammonemic disorders. These two patients appear to represe nt a unique form of congenital hyperinsulinism distinct from the previ ously described autosomal dominant and autosomal recessive variants. W e speculate that the underlying defect involves a site that is common to the amino acid regulation of both insulin secretion in pancreatic b eta-cells and urea synthesis in the liver.