Abstract and Introduction
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of recurrent hypoglycemia in neonates and infants. It is a disorder of glucose homeostasis characterized by unregulated hyperinsulinemia and profound hypoglycemia. PHHI may be differentiated from other causes of hypoglycemia by demonstrating the persistence of inappropriately high insulin levels regardless of blood glucose concentration. Prompt recognition and treatment of PHHI is critical because uncorrected hypoglycemia in the newborn period is associated with permanent damage to the central nervous system and subsequent mental retardation. The aim of therapy is to maintain euglycemia to protect the developing brain from possible damage. Despite recent advances in medical treatment, subtotal pancreatectomy is often necessary. This article will review the function of insulin, glucagon, and somatostatin, pathophysiology of hyperinsulinism, clinical manifestations, differential diagnosis, management, and reported neurologic outcomes of newborns and infants with PHHI.
Persistent hyperinsulinism is a genetically heterogeneous condition associated with excessive insulin production and, although rare, it is the most common cause of severe, persistent hypoglycemia beyond the immediate neonatal period.[1,2,3] It is referred to as persistent hyperinsulinemic hypoglycemia of infancy (PHHI). PHHI was first described more than 40 years ago by McQuarrie[4] and usually presents between birth and the first 3 months of life.[1,2] In a noninbred White population, the estimated frequency is 1 in 50,000 live births[5,6] but in certain populations, such as Saudi Arabia, where approximately 50% of births occur to parents who are first or second cousins, the incidence rises sharply to 1 in 2700 live births.[7,8,9] Previously there was a lack of unifying hypothesis regarding the pathophysiology of the condition, making diagnosis difficult and management strategies problematic. There is increasing evidence, however, that the disorder frequently has a genetic rather than a sporadic origin. Recent investigations suggest that the pathophysiology is commonly caused by genetic defects in the regulation of insulin secretion and generalized beta-cell dysfunction.[10,11] In some infants, recessively inherited mutations have been found in the gene for the plasma membrane sulfonylurea receptor (SUR1) or its associated inwardly rectifying potassium channel (KIR6.2) of the beta[5,12,13,14] Mutations of SUR1 have been found in Ashkenazi Jews and in residents of Saudi Arabia.[7,15,16] Other cases have described a milder, dominantly inherited form of hyperinsulinism that is not linked to the SUR1 locus but is thought to be a mutation in the glucokinase gene.[17,18] A third group of described cases have an unusual combination of congenital hyperinsulinism and hyperammonemia.[10,19] Additionally, several studies have now clearly demonstrated the existence of two forms of hyperinsulinism: diffuse involvement of the pancreatic beta cells or focal adenomatous islet cell hyperplasia.[12,20,21,22,23] However, many sporadic and familial cases of hyperinsulinism remain unexplained.[24]
Patients affected with any of the various forms of hyperinsulinism are at high risk for seizures and permanent brain damage. Early treatment and diagnosis are essential to prevent long-term neurologic sequelae. The aim of therapy is to maintain euglycemia to protect the developing brain from possible damage. Because the cerebral glucose concentration approaches zero when plasma glucose concentration decreases to below 40 mg/dL, blood glucose should be maintained above this level. Traditionally, management has involved initial high rates of glucose infusion (>12 to 15 mg/kg/min) followed by the addition, if needed, of antihypoglycemia medications. Treatment is then dependent on diagnosis. If medical management fails, surgical exploration and nearly total pancreatectomy are indicated.[6]
NAINR. 2003;3(4) © 2003 W.B. Saunders
Cite this: Persistent Hyperinsulinemic Hypogylcemia in Infants - Medscape - Dec 01, 2003.
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