Manifestations of congenital hyperinsulinemic hypoglycemia vary by age and severity of the hypoglycemia. Hypoglycemia in early infancy can cause jitteriness, lethargy, cyanosis, unresponsiveness, hypothermia, or seizures. Milder hypoglycemia in infancy causes hunger every few hours, with increasing irritability or lethargy if feeding is delayed.

Congenital hyperinsulinism often becomes apparent later in the first year of life, sometimes by a failure to tolerate increasing feeding intervals and an inability to sleep through the night. Sometimes an unusual stress like an illness precipitates a severe hypoglycemic episode.

Milder forms have occasionally been detected by investigation of family members of infants with severe forms. Adults with the mildest degrees of congenital hyperinsulinism may simply have a decreased tolerance for prolonged fasting.

The variable ages of presentations and courses suggest that some forms of congenital hyperinsulinism, especially those involving abnormalities of K_ATP channel function, can gradually worsen or improve with time.

The potential harm from hyperinsulinemic hypoglycemia appears to depend on the severity, frequency, and duration. Children who have prolonged or recurrent hyperinsulinemic hypoglycemia in infancy can suffer harm to their brains and may be developmentally delayed.

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