Copyright ©The Author(s) 2023.
World J Gastroenterol. Jul 7, 2023; 29(25): 3932-3963
Published online Jul 7, 2023. doi: 10.3748/wjg.v29.i25.3932
Table 1 Overview of glycogen storage diseases
GSD type (eponym)
Defective enzyme or transporter
Gene location
Primary tissue involvement
Distinctive features
GSD-0GSD-0a: 240600Liver glycogen synthaseGYS2/AR12p12.1LiverNo hepatomegaly. Postprandial hyperglycemia, glycosuria, and hyperlactatemia. Extremely low amount of glycogen in liver tissue
GSD-0b: 611556Muscle glycogen synthaseGYS1/AR19q13.33MuscleCardiac involvement, risk of sudden cardiac arrest
GSD-I (von Gierke)GSD-Ia: 232200Glucose-6-phosphataseG6PC/AR17q.21LiverCoagulopathy, anemia, osteopenia, osteoporosis, renal dysfunction, HA, HCC
GSD-Ib: 232220Glucose-6-phosphatase transporterSLC37A4/AR11q23.3LiverNeutropenia, neutrophil dysfunction, recurrent infections, oral and intestinal mucosal ulcers, IBD, autoimmunity
GSD-II (Pompe)232300Acid α-glucosidaseGAA/AR17q25.3MuscleCardiomyopathy, infantile-onset form. Muscle weakness, late-onset form
Danon disease (formerly GSD-IIb)300257Lysosome-associated membrane protein-2LAMP2/XLDXq24MuscleSkeletal and cardiac myopathy, arrhythmia, intellectual disability
GSD of heart600858AMP-activated protein kinase, γ-2 regulatory subunitPRKAG2/AD7q36.1MuscleSevere ventricular hypertrophy. Electrocardiographic preexcitation and conduction system disease. Premature sudden cardiac death (< 40 yr)
GSD of heart, lethal congenital261740AMP-activated protein kinase, γ-2 noncatalytic subunitPRKAG2/AD7q36.1MuscleSome mutations (R531Q, R384T) cause more severe phenotype. Fetal onset, extreme cardiomegaly, death in infancy
GSD-III (Cori/Forbes)IIIa/IIIb: 232400Glycogen debrancher enzymeAGL/AR1p21.2IIIa: Liver + muscle; IIIb: LiverLiver fibrosis, cirrhosis, HA, HCC (as a complication of cirrhosis). IIIa: Elevated CK, motor developmental delay, myopathy, cardiomyopathy
GSD-IV (Andersen)232500Glycogen branching enzymeGBE1/AR3p12.2LiverClassical hepatic form (rapidly progressive liver disease, HSM, cirrhosis, HCC). Non-progressive hepatic form. Neuromuscular presentation (perinatal, congenital, childhood and adult forms). Myopathy, cardiomyopathy, neuropathy, CNS involvement, APBD. Amylopectin aggregations in liver
GSD-V (McArdle)232600Muscle glycogen phosphorylasePYGM/AR11q13.1MuscleExercise intolerance, muscle cramps, rhabdomyolysis, myoglobinuria, “second wind” phenomenon
GSD-VI (Hers)232700Liver glycogen phosphorylasePYGL/AR14q22.1LiverPhenotypic variability (overlap with GSD-IX). Severe hepatic involvement reported. Mild hypotonia and cardiopathy reported. Excessive glycogen accumulation with structurally normal glycogen in liver tissue. Enzyme deficiency in erythrocytes, leukocytes
GSD-VII (Tarui)232800Muscle phosphofructokinasePFKM/AR12q13.11MuscleExertional myopathy, exercise intolerance, muscle cramps, hemolytic anemia. Rapidly progressive infantile form (multisystem involvement, seizures, cardiomyopathy)
GSD-IXGSD-IXa1 (XLG-1): 306000Phosphorylase kinase, α-subunit, liverPHKA2/XLRXp22.13LiverThe most common subtype. Symptomatic female carriers due to X chromosome inactivation. Clinical symptoms and laboratory abnormalities gradually disappear with age. Severe phenotypes reported
GSD-IXb: 261750Phosphorylase kinase, β-subunitPHKB/AR16q12.1LiverMarked accumulation of glycogen in both liver and muscle. Muscle symptoms are generally mild or absent
GSD-IXc: 613027Phosphorylase kinase, γ-subunitPHKG2/AR16p11.2LiverMore severe phenotype with increased risk for liver fibrosis and cirrhosis
GSD-IXd: 300559Phosphorylase kinase, α-subunit, musclePHKA1/XLRXq13.1MuscleMuscle weakness and muscle cramps during exercise. Mostly in adults
GSD-X261670Muscle phosphoglycerate mutasePGAM2/AR7p13MuscleExercise intolerance, muscle cramps and pain, rhabdomyolysis, myoglobinuria
Fanconi-Bickel syndrome (formerly GSD-XI)227810Glucose transporter 2SLC2A2/AR3q26.2LiverHepatorenal involvement. Proximal renal tubular dysfunction. Osteoporosis/rickets. Different patterns of dysglycemia. Postprandial hyperglycemia and hypergalactosemia
GSD-XI612933Lactate dehydrogenase ALDHA/AR11p15.1MuscleExertional myoglobinuria, easy fatigability, exercise induced myalgia, erythematosquamous skin lesions on the extensor surfaces of the extremities
GSD-XII611881Fructose-1,6-bisphosphate aldolase AALDOA/AR16p11.2MuscleRhabdomyolysis induced by fever and/or exercise, hemolytic anemia with or without myopathy or cognitive dysfunction
GSD-XIII612932Enolase 3 (β-enolase)ENO3/AR17p13.2MuscleExercise intolerance, exercise induced myalgia, muscle weakness
GSD-XV613507Glycogenin-1GYG1/AR3q24MuscleVentricular arrhythmogenic cardiomyopathy, progressive muscle weakness