Glycogen storage disease
|Glycogen storage disease|
A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by enzyme deficiencies affecting either glycogen synthesis, glycogen breakdown or glycolysis (glucose breakdown), typically within muscles and/or liver cells.
GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism (genetically defective enzymes) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid castanospermine.
|Muscle symptoms||Development/ prognosis||Other symptoms|
|GSD 0||Glycogen synthase
|?||Yes||No||No||Occasional muscle cramping||Growth failure in some cases|
|GSD I / GSD 1
(von Gierke's disease)
(G6PC / SLC37A4)
|1 in 50,000 – 100,000||Yes||Yes||Yes||None||Growth failure||Lactic acidosis, hyperuricemia|
|GSD II / GSD 2
(Pompe's disease )
|1 in 40,000 – 50,000.||No||Yes||No||Muscle weakness||*Death by age ~2 years (infantile variant)||Heart failure|
|GSD III / GSD 3
(Cori's disease or Forbes' disease)
|Glycogen debranching enzyme
|1 in 100,000||Yes||Yes||Yes||Myopathy|
|GSD IV / GSD 4
|Glycogen branching enzyme
|1 in 500,000||No||Yes,
|No||Myopathy and dilated cardiomyopathy||Failure to thrive, death at age ~5 years|
|GSD V / GSD 5
|Muscle glycogen phosphorylase
|1 in 100,000 – 500,000||No||No||No||Exercise-induced cramps, Rhabdomyolysis||Renal failure by myoglobinuria, second wind phenomenon|
|GSD VI / GSD 6
|Liver glycogen phosphorylase
Muscle phosphoglycerate mutase
|1 in 65,000 – 85,000||Yes||Yes||Yes ||None||initially benign, developmental delay follows.|
|GSD VII / GSD 7
|1 in 1,000,000||No||No||No||Exercise-induced muscle cramps and weakness||developmental delay||In some haemolytic anaemia|
|GSD IX / GSD 9||Phosphorylase kinase
(PHKA2 / PHKB / PHKG2 / PHKA1)
|?||Yes||Yes||Yes||None||Delayed motor development, Developmental delay|
|GSD X / GSD 10||Enolase 3
|GSD XI / GSD 11||Muscle lactate dehydrogenase
formerly GSD XI / GSD 11, no longer considered a GSD
|GSD XII / GSD 12
(Aldolase A deficiency)
|?||?||In some||?||Exercise intolerance, cramps. In some Rhabdomyolysis.||Hemolytic anemia and other symptoms|
|GSD XIII / GSD 13||β-enolase
|?||?||?||?||Exercise intolerance, cramps||Increasing intensity of myalgias over decades||Serum CK: Episodic elevations; Reduced with rest|
|GSD XV / GSD 15||Glycogenin-1
|Rare||No||No||No||Muscle atropy||Slowly progressive weakness over decades||None|
- Some GSDs have different forms, e.g. infantile, juvenile, adult (late-onset).
- Some GSDs have different subtypes, e.g. GSD1a / GSD1b, GSD9A1 / GSD9A2 / GSD9B / GSD9C / GSD9D.
- GSD type 0: Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems.
- GSD type VIII (GSD 8): In the past it was considered a distinct condition, however it is now classified with GSD type VI or GSD IXa1; it has been described as X-linked recessive inherited.
- GSD type XI (GSD 11): Fanconi-Bickel syndrome, hepatorenal glycogenosis with renal Fanconi syndrome, no longer considered a glycogen storage disease.
- GSD type XIV (GSD 14): Now classed as Congenital disorder of glycosylation type 1 (CDG1T), affects the phosphoglucomutase enzyme (gene PGM1).
- Lafora disease is considered a complex neurodegenerative disease and also a glycogen metabolism disorder.
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Treatment is dependent on the type of glycogen storage disease. E.g. GSD I is typically treated with frequent small meals of carbohydrates and cornstarch to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor.
Overall, according to a study in British Columbia, approximately 2.3 children per 100,000 births (1 in 43,000) have some form of glycogen storage disease. In the United States, they are estimated to occur in 1 per 20,000–25,000 births. Dutch incidence rate is estimated to be 1 per 40,000 births.
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