Snapshot A 16-year-old male presents with fatigue and muscle cramps. He recently tried out for the basketball team and has found himself exhausted soon after performing high-intensity sprints. When resting briefly, he said he gets his “second wind.” After practice, he noticed that his urine was brown. Laboratory results are significant for an elevated creatine kinase level of 1,423 U/L (normal < 200 U/L). There was no increase of lactate on forearm nonischemic testing. (McArdle disease) Introduction Glucose is a crucial source of energy for proper cellular functioning essential for cells without mitochondria e.g., erythrocytes (RBCs) greatly preferred by neurons important energy source for exercising muscle needed for anaerobic glycolysis Serum glucose sources glycogen breakdown gluconeogenesis diet Glycogen storage disorders (GSD) genetic mutations → abnormal glycogen accumulation in certain tissues liver and muscle GSD Defect Findings Management Von Gierke disease (type I) Hepatic glucose-6-phosphatase Autosomal recessive Usually presenting at 3 - 6 months of age Hepatomegaly Signs of hypoglycemia seizure "Doll-like" face Poor growth ↑ uric acid due to impaired renal clearance and increased production gout ↑ lactic acid ↑ triglycerides xanthomas pancreatitis Dietary management frequent small meals avoid fructose, galactose, and sucrose to prevent lactic acidosis Pompe disease (type II) Lysosomal α(1,4)-glucosidase Autosomal recessive Infantile form cardiomegaly generalized muscle hypotonia respiratory distress Juvenile and adult form skeletal myopathy delayed-gross motor development limb-girdle weakness respiratory issues Enzyme replacement therapy alglucosidase alfa Cori disease (type III) Glycogen debranching enzyme Autosomal recessive Most cases involve the muscle and liver Hepatomegaly Mild hypoglycemia intact gluconeogenesis Symptomatic treatment McArdle disease (type V) Muscle glycogen phosphorylase Autosomal recessive Affects the skeletal muscle No elevation of blood lactate during forearm exercise test ↑ creatine kinase Muscle cramp, fatigue, myalgias, myoglobinuria "Second wind" phenomenom rapid relief of fatigue and myalgia secondary to increase blood flow, improved free fatty acid delivery, and liver glucose utilization Sucrose before exercise may improve symptoms Evaluation Von Gierke disease (type I) laboratory testing fastic hypoglycemia elevated lactic acid, triglycerides, uric acid genetic testing preferred over liver biopsy liver biopsy Pompe disease (type II) laboratory testing elevated creatine kinase, lactic acid acid α-glucosidase testing Cori disease (type III) labs depend on organ involvement McArdle disease (type V) laboratory testing elevated creatine kinase (> 1000 U/L) forearm nonischemic testing elevated ammonia, no elevation in lactate no longer recommended histology most cases show no evidence of enzyme activity in muscle fiber when staining for myophosphorylase genetic testing