Ketotic hypoglycemia refers to any circumstance in which low blood glucose is accompanied by ketosis, the presence of ketone bodies (such as beta-hydroxybutyrate) in the blood or urine. This state can be either physiologic or pathologic; physiologic ketotic hypoglycemia is a common cause of hypoglycemia in children, often in response to stressors such as infection or fasting. Pathologic ketotic hypoglycemia is typically caused by metabolic defects, such as glycogen storage disorders.
Causes
Physiologic ketotic hypoglycemia
The body's physiologic response to falling glucose levels is a suppression of insulin secretion from the pancreas, which decreases the amount of glucose available to most tissue but instead prioritizes the remaining amount for the brain. Therefore, the combination of low glucose (hypoglycemia) and the presence of ketone bodies yields the state known as ketotic hypoglycemia. Such a physiologic response is common in adults during periods of fasting, and is particularly common in ill younger children who cannot tolerate long periods of fasting. Episodes of physiologic ketotic hypoglycemia in children decrease with increasing age, presumably because fasting tolerance improves with increasing body mass. Such episodes are rare after the age of nine; persisting episodes past this age should raise suspicion for an underlying pathologic cause. A non-exhaustive list of causes of pathologic ketotic hypoglycemia is listed below:
- Maple syrup urine disease
- Prader-Willi syndrome
- Pyruvate carboxylase deficiency
Idiopathic pathological ketotic hypoglycemia (IPKH) is now a recognized subtype of pathological ketotic hypoglycemia that is characterized by recurrent hypoglycemic episodes with ketosis in pediatric patients after comprehensive evaluation reveals no underlying metabolic or endocrine cause. IPKH patients are often misdiagnosed as physiologically normal patients due to this inconclusive routine testing However, the diagnosis of ketotic hypoglycemia poses a challenge to clinicians, given how nonspecific symptoms can be and given that children in this age range are typically unable to describe their symptoms. Extended fasts should be avoided.