Glycogen storage diseases occur in a variety of subtypes that differ in severity (see Chapter 52). Among the subtypes that result in hypoglycemia, the most severe form is glucose-6-phosphatase deficiency, which is characterized by severe hypoglycemia, massive hepatomegaly, growth retardation, and lactic acidosis. In contrast, deficiencies in the glycogen phosphorylase enzymes may cause isolated hepatomegaly with or without hypoglycemia.
The diagnosis of glycogen storage disease is suggested by a finding of hepatomegaly without splenomegaly. Confirmation of the diagnosis requires specific biochemical studies of leukocytes or liver biopsy specimens. Treatment involves frequent high-carbohydrate feedings during the day and continuous feedings at night via nasogastric tube. Feedings of uncooked cornstarch overnight are sufficient to maintain serum glucose concentrations in some patients.
Defects in gluconeogenesis are uncommon and include fructose-1,6-diphosphatase deficiency and phosphoenolpyruvate carboxykinase deficiency. Affected patients exhibit fasting hypoglycemia, hepatomegaly, lactic acidosis, and hyperuricemia. Ketosis occurs, and FFA and alanine concentrations are high. Treatment involves frequent high-carbohydrate, low-protein feedings (see Chapter 52).
Fatty acid oxidation disorders of ketogenesis include the fatty acid acyl-coenzyme A (CoA) dehydrogenase deficiencies; long-chain, medium-chain, and short-chain acyl-CoA dehydrogenase deficiencies; and hereditary carnitine deficiency (see Chapter 55). Of these disorders, medium-chain acyl-CoA dehydrogenase deficiency is the most common; it occurs in 1 in 9000 to 15,000 live births. Patients often are well in infancy and have the first episode of hypoglycemia at 2 years of age or older. Episodes of hypoglycemia usually occur with prolonged fasting or during episodes of intercurrent illness.
Mild hepatomegaly may be present along with mild hyperammonemia, hyperuricemia, and mild elevations in hepatic transaminases. Ketone concentrations are low or undetected. The diagnosis is confirmed by the finding of elevated concentrations of dicarboxylic acids in the urine. Treatment involves avoidance of fasting.
Many metabolic disorders can lead to hypoglycemia, including galactosemia, hereditary fructose intolerance, and disorders of organic acid metabolism (see Table 172-1). Hypoglycemia in these disorders is usually a reflection of global hepatic dysfunction secondary to the buildup of hepatotoxic intermediates. Many of these disorders present with low concentrations of ketone bodies because ketogenesis also is affected. The finding of non–glucose-reducing substances in the urine suggests a diagnosis of galactosemia or hereditary fructose intolerance. Occurrence of symptoms after ingestion of fructose or sucrose suggests hereditary fructose intolerance. Treatment requires dietary restriction of the specific offending substances.
Hypoglycemia can occur as an adverse effect of numerousmedications (see Table 172-1). Valproate toxicity can cause a disorder similar to that seen in the fatty acid oxidationdefects. Ethanol ingestion also can cause hypoglycemia,especially in younger children, because the metabolism ofethanol results in the depletion of cofactors necessary forgluconeogenesis.