A 3-month-old infant was cranky and irritable, became quite lethargic between feedings, and began to develop a potbelly. A physical examination demonstrated an enlarged liver, while blood work taken between feedings demonstrated elevated lactate and uric acid levels, as well as hypoglycemia. This child most likely has a mutation in which one of the following enzymes?
The child has the symptoms of von Gierke disease, which is caused by a lack of glucose-6-phosphatase activity. In this disorder, neither liver glycogen nor gluconeogenic precursors (e.g., alanine and glycerol) can be used to maintain normal blood glucose levels. The last step (conversion of glucose-6-phosphate to glucose) is deficient for both glycogenolysis and gluconeogenesis. Muscle glycogen cannot be used to maintain blood glucose levels because muscle does not contain glucose-6-phosphatase. A defective liver glycogen phosphorylase (Her disease) will not affect the ability of the liver to raise blood glucose levels by gluconeogenesis. In addition, the lack of liver glycogen phosphorylase does not lead to lactic and uric acid accumulation, although mild fasting hypoglycemia can be observed. Defects in liver glycogen synthase (type 0 glycogen storage disease) will lead to hypoglycemia and hyperketonemia, but not lactate acid or uric acid accumulation. Muscle does not contribute to blood glucose levels, so a defect in muscle glycogen phosphorylase (McArdle disease) will not lead to the observed symptoms but will lead to exercise intolerance. A defect in pyruvate kinase will lead to hemolytic anemia, but not the other symptoms observed in the patient.
Liver glycogen phosphorylase
Glycogen synthase
Glucose-6-phosphatase
Muscle glycogen phosphorylase
Carbohydrates