Differential diagnosis and management of neonatal hypoglycemia

Persistent hypoglycemia in the neonate is most often caused by hyperinsulinemia. Recent discoveries in the molecular and biochemical regulation of insulin secretion have increased dramatically our understanding of disorders responsible for syndromes of hyperinsulinemic hypoglycemia. This article focused on defects and disorders of the K_ATP channel, activating mutation of glucokinase and glutamate dehydrogenase, and other disorders that may be associated with specific phenotypes to permit appropriate targeted therapies. It is essential to evaluate these entities carefully because of the emerging evidence that at least half, if not more, have focal rather than diffuse disease. In the focal disease, localized excision is curative and prevents further hypoglycemia and future long-term hyperglycemia. By contrast, near-total pancreatectomy may be associated with persistent hypoglycemia in the newborn and with a greater risk of hyperglycemia in future years. Delay in diagnosis and appropriate therapy also can result in significant mental retardation. We do not understand the mechanisms or defects in many instances, including the reasons for hyperinsulinemic hypoglycemia with syndromes of perinatal hypoxia and with a specific entity of defective carbohydrate glycosylation. The former condition, however, can be treated successfully with diazoxide and frequent feeding, and the latter responds to supplemental mannose. Despite advances, almost half of all individuals with hyperinsulinemic hypoglycemia are not correctly categorized, which leaves much work for future research.