A 4-month-old white male infant with a temperature of 38.4°C is examined by his pediatrician. His mother indicates that he has had the fever for the past 4 days, been listless, vomiting, and has watery stools. Blood work indicates the infants' blood pH is slightly acidic and shows reduced bicarbonate. Other untoward blood chemistry includes elevated liver enzymes. The child has a protuberant abdomen, thin extremities, and a doll-like face indicative of von Gierke disease. Given this diagnosis, what other deleterious symptom would be expected in this infant?

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Von Gierke disease (Glycogen storage disease type I) is characterized by severe hypoglycemia due to the inability to convert glycogen to glucose, leading to low blood sugar levels.  von Gierke disease (GSDI) results from the absence of glucose-6-phosphatase activity. Patients with von Gierke disease can present during the neonatal period with lactic acidosis and hypoglycemia. The hallmark features of this disease are severe hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. The severity of the hypoglycemia and lactic acidosis can be such that in the past affected individuals died in infancy. Infants often have a doll-like facial appearance due to excess adipose tissue in the cheeks. The metabolic consequences of the hepatic glucose-6-phosphate deficiency of von Gierke disease extend well beyond just the obvious hypoglycemia that results from the deficiency in liver being able to deliver free glucose to the blood. The inability to release the phosphate from glucose 6-phopsphate results in diversion into glycolysis and production of pyruvate as well as increased diversion onto the pentose phosphate pathway. The production of excess pyruvate, at levels above the capacity of the TCA cycle to completely oxidize it, results in its reduction to lactate, leading to lactic acidemia. In addition, some of the pyruvate is transaminated to alanine, leading to hyperalaninemia. Some of the pyruvate, which cannot be fully oxidized in the TCA cycle, will be oxidized to acetyl-CoA and so the acetyl-CoA will end up in the cytosol, where it will serve as a substrate for triglyceride and cholesterol synthesis resulting in hyperlipidemia. The oxidation of glucose 6-phophate via the pentose phosphate pathway leads to increased production of ribose 5-phosphate, which then activates the de novo synthesis of the purine nucleotides. In excess of the need, these purine nucleotides will ultimately be catabolized to uric acid, resulting in hyperuricemia and consequent symptoms of gout.

A 4-Month-Old White Male Infant with a Temperature of 38