Causes of hypoglycemia in infants and children
- Agneta Sunehag, MD, PhD
Agneta Sunehag, MD, PhD
- Associate Professor of Pediatrics
- Baylor College of Medicine
- Morey W Haymond, MD
Morey W Haymond, MD
- Professor of Pediatric Nutrition
- Baylor College of Medicine
Hereditary disorders caused by a deficiency of specific enzymes involved in mobilization, interconversion, or utilization of metabolic substrates frequently are associated with hypoglycemia (table 1) . These enzymatic defects may involve carbohydrate, amino acid, or fat metabolism and are individually rare; almost all are inherited as autosomal recessive traits. Because of the interactions of fat, carbohydrate, and amino acid metabolism in the maintenance of normal fuel homeostasis, abnormalities in the metabolism of a single substrate can have primary and secondary effects on other metabolic pathways. A common expression of these derangements is the development of biochemical or symptomatic hypoglycemia. If hypoglycemia is not promptly recognized in children, they may develop symptoms and suffer permanent neurologic sequelae.
The etiology of hypoglycemia in infants and children will be presented here. The approach to hypoglycemia in infants and children and to hypoglycemia in neonates is discussed separately. (See "Approach to hypoglycemia in infants and children" and "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia".)
For hypoglycemia to occur, the rate of appearance of glucose into the plasma space must be less than its rate of utilization. This can be due to defective glucose production, increased glucose utilization, or some combination of the two. In many cases of hypoglycemia, a clear pathophysiologic mechanism cannot be assigned. However, we would encourage the reader to envision mechanisms that would lead to an imbalance in the rate of glucose production and/or glucose utilization based on known physiologic principles that we believe are fundamental to glucose homeostasis in infants, children, and young adults .
DISORDERS OF CARBOHYDRATE METABOLISM
Disorders of carbohydrate metabolism that can lead to hypoglycemia include deficiencies of hepatic enzymes in the pathways of the metabolism of glycogen (table 2 and table 3), galactose, and fructose.
The time of onset of hypoglycemia in relation to the last meal may provide a clue to the diagnosis. Patients with galactosemia or hereditary fructose intolerance become hypoglycemic within several hours of ingestion of galactose or fructose, respectively. Patients with hepatic enzyme deficiencies of glycogenolysis and gluconeogenesis typically become symptomatic between 2 and 20 hours after the last meal.
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- DISORDERS OF CARBOHYDRATE METABOLISM
- Disorders of glycogenolysis
- - Glycogen synthetase deficiency
- - Glucose-6-phosphatase deficiency
- - Debrancher deficiency
- - Hepatic phosphorylase deficiency
- - Hepatic phosphorylase b kinase deficiency
- Disorders of glycosylation
- - Phosphoglucomutase 1 deficiency
- Disorders of gluconeogenesis
- - Fructose 1,6, bisphosphatase deficiency
- - Pyruvate carboxylase deficiency
- - PEPCK deficiency
- Hereditary fructose intolerance
- DISORDERS OF AMINO ACID METABOLISM
- DISORDERS OF FATTY ACID METABOLISM
- Clinical features
- INCREASED UTILIZATION OF GLUCOSE
- - Endogenous
- - Exogenous
- MISCELLANEOUS CAUSES
- Ketotic hypoglycemia
- Hormone deficiencies
- - Oral hypoglycemics
- - Ethanol
- - Salicylates
- - Beta blockers
- - Pentamidine
- Heart disease
- Other causes