Physical Examination (Pertinent Findings): JS appears sleepy and feels clammy to the touch. His respiratory rate is elevated. His temperature is normal. JS has a protuberant, firm abdomen that appears to be nontender. His liver is palpable 4 cm below the right costal margin and is smooth. His kidneys are enlarged and symmetrical.
Pertinent Test Results:
H = High; L = Low.
JS is sent to the regional children’s hospital for further evaluation. Ultrasound studies confirm hepatomegaly and renomegaly and show no evidence of tumors. A liver biopsy is performed. The hepatocytes are distended. Staining reveals large amounts of lipid (primarily triacylglycerol) and carbohydrate. Liver glycogen is elevated in amount and normal in structure. Enzyme assay using liver homogenate treated with detergent reveals <10% of the normal activity of glucose 6-phosphatase, an enzyme of the endoplasmic reticular (ER) membrane in the liver and the kidneys.
Diagnosis: JS has glucose 6-phosphatase deficiency (glycogen storage disease [GSD] type Ia, von Gierke disease).
Treatment (Immediate): JS was given glucose intravenously, and his blood glucose level rose into the normal range. However, as the day progressed, it fell to well below normal. Administration of glucagon had no effect on blood glucose levels but increased blood lactate. JS’s blood glucose levels were able to be maintained by constant infusion of glucose.
Prognosis: Individuals with glucose 6-phosphatase deficiency develop hepatic adenomas starting in the second decade of life and are at increased risk for hepatic carcinoma. Kidney glomerular function is impaired and can result in kidney failure. Patients are at increased risk for developing gout, but this rarely occurs before puberty.
Nutrition Nugget: Long-term medical nutrition therapy for JS is designed to maintain his blood glucose levels in the normal range. Frequent (every 2–3 hours) daytime feedings rich in carbohydrate (provided by uncooked cornstarch that is slowly hydrolyzed) and nighttime nasogastric infusion (pump assisted) of glucose are advised. Avoidance of fructose and galactose is recommended because they are metabolized to glycolytic intermediates and lactate, which can exacerbate the metabolic problems. Calcium and vitamin D supplements are prescribed.
Genetics Gem: GSD Ia is an autosomal-recessive disorder caused by >100 known mutations to the gene for glucose 6-phosphatase located on chromosome 17. It has an incidence of 1:100,000 and accounts for ~25% of all cases of GSD in the United States. It is one of the few genetic causes of hypoglycemia in newborns. GSD Ia is not routinely screened for in newborns. [Note: Deficiency of the translocase that moves glucose 6phosphate into the ER is the cause of GSD Ib. Hypoglycemia and neutropenia are seen.]
Review Questions: Choose the ONE best answer.
RQ1. JS is hypoglycemic because:
A. free (nonphosphorylated) glucose cannot be produced from either glycogenolysis or gluconeogenesis as a result of the deficiency in glucose 6-phosphatase.
B. glycogen phosphorylase is dephosphorylated and inactive, and glycogen cannot be degraded.
C. hormone-sensitive lipase is dephosphorylated and inactive, and fatty acid substrates for gluconeogenesis cannot be generated.
D. the decrease in the insulin/glucagon ratio upregulates glucose transporters in the liver and kidneys, resulting in increased uptake of blood glucose.