Congenital hyperinsulinism (HI) is the most common cause of severe and persistent hypoglycemia in infancy. Both autosomal dominant (AD) and autosomal recessive (AR) forms are known to exist. This report describes two patients with congenital HI combined with hyperammonemia (HA).
Patient 1 is a 5 yr old boy of Northern European descent who presented at age 7 months with hypoglycemic seizures and was found to have elevated insulin and ammonia levels. Patient 2 is a 7 yr old Sephardic Jewish boy who underwent an evaluation at age 6 months for persistent seizures and hypotonia, at which time he was found to have hypoglycemia and hyperammonemia. An intravenous leucine tolerance test induced hypoglycemia, and histology from subtotal pancreatectomy revealed diffuse islet cell dysplasia. At the time of hypoglycemia, both patients demonstrated features consistent with hyperinsulinism: an inadequate rise in serum ketones and an inappropriate glycemic response to glucagon (delta glucose = 48 mg/dl in Pt 1 and 71 mg/dl in Pt 2). The hypoglycemia in both patients responded to high-dose diazoxide. The serum ammonia levels were persistently elevated in the 150-200 umol/l range (normal < 33 umol/l), and did not decrease with protein restriction or increase with protein loading. In both patients plasma amino acids were notable for normal alanine, glycine, citrulline, ornithine, lysine, glutamate, and glutamine levels. Urine orotic acid levels were normal in both patients. NAG and CPS synthetase activities determined in liver from Patient 2 were normal.
