Laboratory Studies
The extent and severity of biochemical abnormalities vary in children with glycogen storage disease type VI (GSD VI), also known as Hers disease. Blood glucose levels should be assessed; after a short fast (3-5 hours), mild hypoglycemia may develop in younger patients.
Levels of urine ketones and serum ketone bodies (eg, acetoacetate, beta-hydroxybutyrate) may be elevated during a short fast and are proportional to the degree of fasting. Mild hyperlipidemia may be present, with serum cholesterol elevations higher than serum triglycerides. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels may be mildly elevated. Other liver function test findings are usually normal in the absence of cirrhosis.
Patients with proximal renal tubule acidosis may have increased urine pH levels with abnormal levels of calcium, phosphate, and amino acids and decreased blood pH levels with a normal anion gap.
Imaging Studies
Liver volume quantitation may be performed using abdominal MRI or CT scanning.
Other Tests
Evaluation of a patient with suspected GSD VI requires monitored assessment of fasting adaptation in an inpatient setting. After 3-5 hours of fasting, patients with GSD VI typically exhibit hypoglycemia with a normal serum lactic acid level. This same pattern occurs in patients with glycogen storage disease type 0 (GSD 0), glycogen storage disease type III (GSD III), and hereditary fructose intolerance (HFI). HFI can be identified via development of hypoglycemia and increased lactic acid after oral fructose loading.
A fasted glucagon challenge may further narrow the field of diagnostic possibilities. Patients with GSD VI may have a normal hyperglycemic response without change in lactic acid after glucagon administration, although results may be inconclusive.
Molecular diagnostic testing for a specific mutation in the PYGL gene may be used to identify carriers and affected children in the Mennonite population.
Procedures
Definitive diagnosis of GSD VI requires a liver biopsy and enzyme assay. Histologic examination and determination of glycogen content may also be performed.
An enzyme assay can be performed in more easily obtainable cells, including RBCs and WBCs. However, owing to the presence of isoenzymes, normal enzyme activity in these cells does not exclude the possibility of isolated hepatic involvement in an affected patient.
Histologic Findings
Histologic analysis of the liver typically reveals glycogen-distended hepatocytes. The accumulated glycogen (ie, alpha particles, rosette form) appears frayed or burst and is less compact than the glycogen present in glycogen storage disease type I or III. Interlobular fibrous septa and low-grade inflammatory changes may be seen. Liver glycogen content may also be increased as much as 4-fold, although muscle glycogen remains normal in structure and quantity.
