Glycogen Storage Diseases

GSD type	Deficiency	Key clinical findings	Diagnosis	Therapy
GSD 0a	Glycogen synthase 2	Ketotic hypoglycemia, no hepatomegaly	Liver biopsy and enzyme testing, DNA testing	Uncooked cornstarch, commercial glucose polymers, liver transplantation
GSD 0b	Muscle glycogen synthase	Cardiomyopathy, exercise intolerance, weakness	Muscle biopsy (glycogen depletion), enzyme assay, DNA testing	No specific treatment
GSD I (von Gierke disease)	glucose-6-phosphatase	Ketotic hypoglycemia, hepatomegaly	DNA testing, liver biopsy, enzyme assay	Uncooked cornstarch, allopurinol, G-CSF, commercial glucose polymers, liver transplantation
GSD II* (Pompe disease)	Lysosomal acid maltase	Hypotonia, muscle weakness, hypertrophic cardiomyopathy, rhabdomyolysis	Fibroblast, leukocyte, muscle, or liver enzyme assay, DNA testing	Enzyme replacement therapy, commercial glucose polymers, liver transplantation
GSD IIb* (Danon disease)	Lysosome-associated membrane protein 2	Hypotonia, hypertrophic cardiomyopathy, rhabdomyolysis	Muscle biopsy, DNA testing	No specific treatment
GSD III	glycogen debrancher	Ketotic hypoglycemia, hepatomegaly	Fibroblast or liver enzyme assay, DNA testing	Uncooked cornstarch, commercial glucose polymers, liver transplantation
GSD IV	glycogen branching enzyme	Hepatomegaly, cirrhosis, rare neuromuscular presentations	Fibroblast, muscle, or liver biopsy, DNA testing	Commercial glucose polymers, liver transplantation
GSD V (McArdle disease)	muscle phosphorylase	Fatigability, myoglobinuria, rhabdomyolysis	Muscle biopsy, muscle enzyme assay, DNA testing	Sucrose prior to exercise
GSD VI (Hers disease)	liver phosphorylase	Hepatomegaly, mild hypoglycemia	Liver biopsy and enzyme assay, DNA testing	Commercial glucose polymers, liver transplantation
GSD VII (Tarui disease)	phosphofructokinase deficiency	Fatigability, myoglobinuria, rhabdomyolysis	Muscle enzyme assay, DNA testing	No specific treatment
Phosphoglycerate kinase deficiency	Phosphoglycerate kinase	Hemolysis, fatigability, myoglobinuria, CNS dysfunction, rhabdomyolysis	Muscle/RBC enzyme assay, DNA testing	Bone marrow transplantation
GSD IX	phosphorylase kinase	Hepatomegaly, mild hypoglycemia, fatigability, exercise intolerance	Liver/muscle biopsy, enzyme assay, DNA testing	Commercial glucose polymers, liver transplantation
GSD X	phosphoglycerate mutase	Fatigability, myoglobinuria, exercise intolerance, rhabdomyolysis	Muscle biopsy and enzyme assay, DNA testing	No specific treatment
GSD XI	lactate dehydrogenase A and B	Fatigability, myoglobinuria, rhabdomyolysis	Muscle or RBC enzyme assay, DNA testing	No specific treatment
GLUT2 deficiency (Fanconi-Bickel syndrome)	GLUT2	Growth retardation, renal Fanconi syndrome, galactosemia	Clinical features, DNA testing	Frequent, small meals, uncooked cornstarch or nocturnal enteral nutrition, electrolytes, carnitine, and vitamin D as needed, restriction of galactose
GSD XII	aldolase A	Hemolysis, jaundice, myoglobinuria, muscle weakness, fatigability, rhabdomyolysis	Muscle or RBC enzyme assay, DNA testing	No specific treatment
GSD XIII	beta-enolase	Exercise intolerance, increased CPK, rhabdomyolysis	Muscle biopsy, enzyme assay, DNA testing	No specific treatment
GSD XIV	phosphoglucomutase 1	Exercise intolerance, myoglobinuria, increased CPK, rhabdomyolysis, myoglobinuria	Muscle biopsy, enzyme assay, DNA testing	No specific treatment
GSD XV	glycogenin 1	Muscle weakness, arrhythmias	Muscle biopsy (glycogen depletion), DNA testing	No specific treatment
* Initially, these diseases were categorized as GSDs. Later, it was discovered that the buildup of glycogen in lysosomes that is observed in these diseases is caused by impaired lysosomal metabolism, rather than a lack of energy from glycogen/glucose metabolism. As a result, these conditions are now viewed as both GSDs and lysosomal storage diseases.