What is Glycogen Storage Disease (GSD)?

• Inborn errors of glycogen metabolism that result from pathogenic variants in genes for the proteins involved in glycogen synthesis, degradation, or regulation.
• Glycogen is most abundant in the liver and muscle, which are most affected by these disorders.
  • Liver: glycogen is the main source of energy, especially in muscle.
  • The main manifestations of GSDs are muscle crumps, exercise intolerance and easy fatigability, and progressive weakness.

Type	Alternative names/subtypes	Affected enzyme	Gene/location	Inheritance	Organ	Frequency	Signs	OMIM
0	0a	Liver glycogen synthase	GYS2 12p12.1	AR	Liver	Unknown (rare)	Hypoglycemia Morning fatigue Ketosis Convulsion Variable signs and symptoms No hepatomegaly	240600
	0b	Muscle glycogen synthase	GYS1 19q13.33	AR	Muscle (Lack of glycogen in muscle)	Unknown (rare)	Exercise intolerance Hypertrophic cardiomyopathy Fainting	611556
I	Ia; von Gierke	Glucose-6-phosphate	G6PC 17q21	AR	Liver, Kidney Intestine	1/125,000	Hypoglycemia Lactic acidosis Hyperuricemia Hyperlipidemia Hepatomegaly (abdominal distension) Osteoporosis Kidney disease Hypoglycemic seizures and related changes Hepatic adenomas and carcinoma Endocrine disorders Short stature Pulmonary hypertension-heart failure Anemia	232200
	Ib; von Gierke	Glucose-6-phosphate transporter	SLC37A4 11q23	AR	Liver, Kidney Intestine Neutrophil	1/500,000	Same as Type Ia with Neutropenia (recurrent infections) Inflammatory bowel disease Dental diseases	232200
II	Pompe	Acid α-glucosidase (lysosomal enzyme) – it is also lysosomal storage disease!	GAA	AR	Muscle Heart	1/40,000	Myopathy, hypotonia/muscle weakness, hepatomegaly, hypertrophic cardiomyopathy	232220
III	Cori/Forbes	Glycogen debranching enzyme	AGL		Liver, Muscle Heart	1/100,000	Hypoglycemia, ketosis, hepatomegaly, myopathy, cirrhosis	232400
IV	Anderson	Glycogen branching enzyme	GBE1		Heart Liver	1/600,000	Hepatomegaly, liver dysfunction/cirrhosis, myopathy, rare neuromuscular (fetal akinesia, azonal neuropathy, adult polyglucosan body disease)	232500
V	McArdle	Muscle glycogen phosphorylase	PYGM		Muscle		Fatigue, myoglobinuria, rhabdomyolysis	232600
VI	Hers	Liver glycogen phosphorylase	PYGL		Liver		Hepatomegaly, mild hypoglycemia	232700
VII	Tarui	Muscle phosphofructose kinase	PFKM		Muscle		Fatigue, myoglobinuria, rhabdomyolysis	232800
IX	IXa	Phosphorylase kinase (α2 subunit)	PHKA2				Hepatomegaly Mild hypoglycemia Fatigability Exercise intolerance	306000
	IXb	Phosphorylase kinase (β subunit)	PHKB					261750
	IXc	Phosphorylase kinase (γ subunit)	PHKG2					613027
	IXd	Phosphorylase kinase (α1 subunit)	PHKA1					300559
X	–	Muscle phosphoglycerate mutase	PGAM2				Fatigability Myoglobinuria Exercise intolerance Rhabdomyolysis	261670
XI	Fanconi-Bickel	Glucose transporter 2	SLC2A2					227810
XII	–	Aldolase A	ALDOA					611881
	–	β-Enolase	ENO3					612932
	–	Glycogenin-1	GYG1					603942
Danon disease (GSD IIb)		Lysosomal-associated membrane protein 2	LAMP2		Muscle Heart		Hypotonia hypertrophic cardiomyopathy rhabdomyolysis	300257
Lafora disease	2A	Laforin	EPM2A					254780
Lafora	2B	Malin	NHLRC1					245780