Glycogen Storage Disease Type 0

Inborn error of metabolism of glucose caused by decreased glycogen synthetase activity and characterized by fasting hypoglycemia with ketosis beginning in early infancy. Unlike other GSDs, GSD 0 does not result in tissue accumulation of normal or abnormal glycogen.

Glycogen Synthetase Deficiency.

Less than 1:250,000 live births.

Autosomal recessive trait. Male-to-female ratio is 1:1. Disease is caused by a defect in the gene coding for liver glycogen synthetase (GYS2), which is located on chromosome band 12p12.2.

A decrease or absence of hepatic glycogen synthetase, which is the rate-limiting enzyme for glycogen synthesis, by transferring glucose units from UDP-glucose to a glycogen primer. This action depends on phosphorylation/dephosphorylation mechanisms and is regulated by several hormones, including insulin, epinephrine, and glucagon. Secondary to a lack of storage of glycogen, GSD 0 patients develop hypoglycemia in the early stages of fasting, when the main source of glucose is provided by glycogenolysis, while gluconeogenesis is not able to maintain normoglycemia. On the other hand, feeding results in postprandial hyperglycemia and increased blood lactate levels because glycogen synthesis is very limited; excess glucose mainly undergoes lactate conversion through the glycolytic pathway. Muscle glycogen synthetase is coded by a different gene and is not affected in patients with GSD 0.

After 5 to 7 hours of fasting, patients demonstrate hypoglycemia and ketosis (and ketonuria), while lactate and alanine levels remain normal. Injection of glucagon fails to elicit a rise in plasma glucose in fasted patients, whereas after a meal, it elicits hyperglycemia and decreased levels of plasma lactate and alanine. Oral intake of glucose, fructose, or galactose elicits a consistent rise in blood lactate. Definitive diagnosis of GSD 0 requires a liver biopsy for enzyme assay (defective glycogen synthetase activity) and microscopic analysis (decreased amounts of normal glycogen stores, increased fat accumulation).

Early-onset symptomatic hypoglycemia in infancy, commonly presenting as seizures, disorientation, abnormal eye movements, and/or coma occurring in the morning before breakfast or after inadvertent fasting. Mild forms may display less suggestive signs, such as drowsiness, lethargy, mental confusion, sweating, pallor, attention deficit, and headache. Evolution is characterized by growth retardation. Physical examination may reveal mild hepatomegaly.

Preoperative examination of a child with GSD 0 must document the presence or absence of hepatomegaly, lactic acidosis, hyperketosis or hypoketosis, and associated signs of hepatic insufficiency. The characteristic schedule of hypoglycemia following fasting (delay, intensity, predictability, precipitating factors) should be closely evaluated; this can be achieved only by monitored assessment of fasting adaptation in an inpatient setting. Outpatient surgery is contraindicated in GSD 0 patients. Evaluate serum electrolytes to calculate the anion gap, thus determining the existence of metabolic acidosis (which is absent in typical GSD 0 patients). Evaluate liver enzymes; mild elevations of aspartate aminotransferase and alanine aminotransferase are consistent with mild hepatocellular damage.

Aim to maintain normal intake of carbohydrate by intravenous glucose infusion during the perioperative period (including preoperative fasting period). Main risk is the development of severe perioperative hypoglycemia. Establish infusion of dextrose preoperatively to maintain normal carbohydrate intake (may require 20% dextrose). Maintain good hydration status. Avoid fasting, even short fasting, with early establishment of enteral feeding postoperatively if possible. Monitor blood glucose and blood gases; place arterial catheter for longer cases.

No agents specifically contraindicated.

Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance): Severe autosomal recessive inherited inborn error of metabolism of glucides as a result of a deficiency of hepatic fructose 1-aldolase. Becomes apparent only when fructose is ingested and is characterized by vomiting, hypoglycemia, severe metabolic acidosis, coma, growth retardation (even cachexia), hepatomegaly, jaundice, coagulopathy, and renal Fanconi syndrome. Gene map locus is 9q22.3.

Glycogen Storage Disease Type I (GSD I): Severe inborn liver dysfunction caused by an almost total deficiency of hepatic glucose-6-phosphatase (type Ia) or defect in intracellular transport of the enzyme substrate (type Ib), resulting in severe hypoglycemia and its consequences (seizures, cyanosis, apnea).