Neonatal and childhood hypoglycemia will be considered together, although some are of the fasting type and some are postprandial.

Idiopathic hypoglycemia of infancy. It has been reported that as many as 10% of all neonates have at least one low blood glucose value. Neonatal reference values are lower than the adult reference range, and there is disagreement as to what level should be considered hypoglycemic. Values considered hypoglycemic in the literature range from 20-40 mg/100 ml (1.10-2.20 mmol/L). The most widely quoted reference value lower limits are 20 mg/100 ml for premature or low-birth-weight newborns and 30mg/100 ml for term normal-weight newborns during the first day of life. These values were originally derived from whole blood assay. Conversion to serum or plasma glucose assay values (15% higher than whole blood) would bring the premature lower limit on serum specimens to about 25 mg/100 ml (1.38 mmol/L) and the mature infant lower limit on serum to about 35 mg/100 ml (1.93 mmol/L). The other frequently used reference range consists of premature infant serum lower limit of 30 mg/100 ml (1.65 mmol/L) and mature infant serum lower limit of 40 mg/100 ml (2.20 mmol/L) during the first day of life. Use of these reference values results in at least 10% more diagnoses of hypoglycemia than use of the lower reference limits. Since a substantial number of these infants are asymptomatic, the lower values are more commonly used. In both systems, the serum glucose lower limit after the first day of life is 40 mg/100 ml. Idiopathic neonatal hypoglycemia is more common in male infants with low birth weight for age and in premature infants. In some cases the condition is aggravated by delay in beginning milk feeding. Clinical symptoms occur within 72 hours of birth and include some combination of tremors, twitching, cyanosis, respiratory difficulties, high-pitched or weak cry, refusal to eat, limpness, apnea, and convulsions. These symptoms are nonspecific and could be due to a wide variety of serious or life-threatening neonatal illnesses.

Neonatal hypoglycemia is thought to be caused at least in part by low hepatic glycogen levels. The condition is usually transient and is treated by oral milk and glucose (if mild) or by parenteral glucose (if severe). If the infant does not develop a clinical problem until after milk feeding is begun and the problem continues, the possibility of leucine sensitivity should be considered.

Leucine sensitivity. Symptoms of leucine sensitivity usually begin within the first 2 years of life and spontaneously disappear by age 5-6 years. Intake of foods that are rich in the amino acid leucine (e.g., cow’s milk) apparently stimulate the pancreatic beta cells to overproduce insulin, rather similar to the effect of tolbutamide. The patients typically have a low FBG level and demonstrate marked hypoglycemia after leucine administration. Diagnosis is made by a leucine tolerance test, similar to the OGTT but using oral leucine. Since leucine also stimulates 50%-70% of insulinomas, the possibility of insulin-producing tumor or nesidioblastosis must also be considered.

Nesidioblastosis. Occasionally children with hypoglycemia have diffuse pancreatic islet cell hyperplasia known as nesidioblastosis. Insulinomas also occur but are rare. Diagnosis is the same as for insulinomas and is based on demonstrating inappropriate elevation of insulin when blood glucose levels are low.

Galactosemia. Galactosemia is an inborn error of metabolism produced by deficiency of an enzyme necessary to metabolize galactose to glucose. Galactose is produced by metabolism of lactose, which is present in milk. Some of these patients develop hypoglycemic episodes, presumably due to abnormality of liver production of glucose from glycogen. A more complete summary of this condition, including laboratory diagnosis, is found in Chapter 34.

Ketosis. Ketosis said to be the most common etiology of hypoglycemia in childhood. Onset is usually between age 1.5 and 5 years, and the condition usually disappears by age 10 years. It is more common in males of lower than normal birth weight. Episodes of hypoglycemia tend to be precipitated by prolonged lack of food intake or by a low-calorie, low-carbohydrate diet. The cause is thought to be at least partially due to depletion of hepatic glycogen. The child is normal between episodes. Hypoglycemic attacks are usually associated with readily detectable plasma ketone bodies and frequently with urine ketonuria. Blood glucose levels and plasma insulin values are both low.

Other. Hypoglycemia may be associated with maternal toxemia of pregnancy, poorly controlled diabetes mellitus, neonatal severe hypoxia, or neonatal sepsis. Diagnosis would be based on recognition that these conditions are present.