A 4-month-old Caucasian 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 infant is hypoglycemic but this condition does not respond to either epinephrine or glucose administration. In addition, his blood pH is slightly acidic and shows reduced bicarbonate. Other untoward blood chemistry includes elevated triglycerides, cholesterol, and liver enzymes. The child has a protruberant abdomen, thin extremities, and a doll-like face. The pediatrician suspects a specific condition and orders a liver biopsy to test for the activity of which of the following enzyme activities?
(A) glucose-6-phosphatase
(B) glycogen synthase
© muscle phosphofructokinase
(D) muscle phosphorylase
(E) pyruvate kinase
Explanation
(A) Deficiency in glucose-6-phosphatase (choice A) is one cause of glycogen storage disease type I (specifically type Ia, von Gierke disease). Hallmarks of the disease are hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. If symptoms do not appear until the third or fourth month they include hepatomegaly and hypoglycemic seizures. Afflicted children have a protruberant abdomen due to the massive hepatomegaly. Outward physical signs also include extremely thin extremities, short stature, and chubby doll-like faces. Liver glycogen synthase deficiency (choice B) presents with morning fatigue and ketotic hypoglycemia on fasting—both of which rapidly disappear on feeding. Symptoms can be rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and nighttime feedings of suspensions of uncooked corn starch. Adeficiency in muscle phosphofructokinase (choice C) results in glycogen storage disease type VII (Tarui disease). Clinically, the symptoms seen in Tarui disease are very similar to those seen in muscle phosphorylase deficiency (choice D), glycogen storage disease type V (McArdle disease) such as exercise-induced cramping and early fatigue. There are five clinical characteristics allowing distinction betweeen Tarui and McArdle disease: exercise intolerance is evident in childhood and more severe and is associated with nausea and vomiting; the intolerance is particularly acute following meals rich in carbohydrates; hyperuricemia is more severe; compensated hemolytic anemia is evidenced by increased serum bilirubin and reticulocyte count, and lastly; an abnormal polysaccharide is present in muscle fibers. Deficiency in PK (choice E) is the most common enzyme deficiency leading to hemolytic anemia and the disorder is characterized by lifelong episodes. The most severe deficiency will result in embryonic lethality.