Glycogen storage disease

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(Redirected from Dextrinosis)


Glycogen Storage Disease (GSD)[edit | edit source]

The molecular structure of glycogen, central to understanding Glycogen Storage Diseases.

Glycogen Storage Disease (GSD), also known as glycogenosis and dextrinosis, refers to a group of metabolic disorders characterized by enzyme deficiencies affecting glycogen synthesis, glycogen breakdown, or glycolysis (the breakdown of glucose).

typically in muscles and/or liver cells.[1]

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.[2]

Types[edit | edit source]

Type
(Eponym)
Enzyme deficiency
(Gene[3])
Incidence (births) Hypo-
glycemia
?
Hepato-
megaly
?
Hyperlip-
idemia
?
Muscle symptoms Development/ prognosis Other symptoms
GSD 0 Glycogen synthase
(GYS2)
? Yes No No Occasional muscle cramping Growth failure in some cases
GSD I / GSD 1
(von Gierke's disease)
Glucose-6-phosphatase
(G6PC / SLC37A4)
1 in 50,000 – 100,000[4][5] [6] Yes Yes Yes None Growth failure Lactic acidosis, hyperuricemia
GSD II / GSD 2
(Pompe disease )
Acid alpha-glucosidase
(GAA)
1 in 13,000. [7] No Yes No Muscle weakness Progressive proximal skeletal muscle weakness with varied timeline to threshold of functional limitation (early childhood to adulthood). Approximately 15% of the Pompe population is classified as infantile Pompe which is typically deadly within the first year if untreated. Heart failure (infantile), respiratory difficulty (due to muscle weakness)
GSD III / GSD 3
(Cori's disease or Forbes' disease)
Glycogen debranching enzyme
(AGL)
1 in 100,000 Yes Yes Yes Myopathy
GSD IV / GSD 4
(Andersen disease)
Glycogen branching enzyme
(GBE1)
1 in 500,000[8] No Yes,
also
cirrhosis
No Myopathy and dilated cardiomyopathy Failure to thrive, death at age ~5 years
GSD V / GSD 5
(McArdle disease)
Muscle glycogen phosphorylase
(PYGM)
1 in 100,000 – 500,000[9][8] No No No Exercise-induced cramps, Rhabdomyolysis Renal failure by myoglobinuria, second wind phenomenon
GSD VI / GSD 6
(Hers' disease)
Liver glycogen phosphorylase
(PYGL)
Muscle phosphoglycerate mutase
(PGAM2)
1 in 65,000 – 85,000[10] Yes Yes Yes [11] None initially benign, developmental delay follows.
GSD VII / GSD 7
(Tarui's disease)
Muscle phosphofructokinase
(PKFM)
1 in 1,000,000[12] 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 Phosphoglycerate mutase

(PGAM2)

? ? ? ? Exercise-induced muscle cramps and weakness Myoglobinuria[13]
GSD XI / GSD 11 Muscle lactate dehydrogenase
(LDHA)
? ? ? ?
Fanconi-Bickel syndrome
formerly GSD XI / GSD 11, no longer considered a GSD
Glucose transporter
(GLUT2)
? Yes Yes No None
GSD XII / GSD 12
(Aldolase A deficiency)
Aldolase A
(ALDOA)
? No In some No Exercise intolerance, cramps. In some Rhabdomyolysis. Hemolytic anemia and other symptoms
GSD XIII / GSD 13 β-enolase
(ENO3)
? No ? No Exercise intolerance, cramps Increasing intensity of myalgias over decades[14] Serum CK: Episodic elevations; Reduced with rest[14]
GSD XV / GSD 15 Glycogenin-1
(GYG1)
Rare[15] No No No Muscle atropy Slowly progressive weakness over decades None

Remarks:

  • 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.[3]
  • 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,[16] however it is now classified with GSD type VI[17] or GSD IXa1;[18] it has been described as X-linked recessive inherited.[19]
  • GSD type XI (GSD 11): Fanconi-Bickel syndrome, hepatorenal glycogenosis with renal Fanconi syndrome, no longer considered a glycogen storage disease.[3]
  • GSD type XIV (GSD 14): Now classed as Congenital disorder of glycosylation type 1 (CDG1T), affects the phosphoglucomutase enzyme (gene PGM1).[3]
  • Lafora disease is considered a complex neurodegenerative disease and also a glycogen metabolism disorder.[20]

Diagnosis[edit | edit source]

Micrograph of glycogen storage disease with histologic features consistent with Cori disease. Liver biopsy. H&E stain.


Treatment[edit | edit source]

Treatment is dependent on the type of glycogen storage disease. GSD I is typically treated with frequent small meals of carbohydrates and cornstarch, called modified cornstarch therapy, to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor.[21]

Epidemiology[edit | edit source]

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.[22] In the United States, they are estimated to occur in 1 per 20,000–25,000 births.[4] Dutch incidence rate is estimated to be 1 per 40,000 births. While a Mexican incidence showed 6.78:1000 male newborns.[23][24]


Types of GSD[edit | edit source]

GSD is categorized into different types based on the enzyme deficiency and affected tissues:

  • Type I (Von Gierke Disease): Affects glucose release from the liver.
  • Type II (Pompe Disease): Involves muscle and liver glycogen breakdown.
  • Type III (Cori or Forbes Disease): Affects liver and muscle glycogen breakdown.
  • Others: There are several other types, each with specific enzyme deficiencies.

Causes[edit | edit source]

GSDs are caused by genetic mutations that result in the deficiency of enzymes responsible for glycogen metabolism. These are typically inherited in an autosomal recessive pattern.

Symptoms[edit | edit source]

Symptoms vary depending on the type of GSD but may include:

  • Hypoglycemia (low blood sugar)
  • Muscle weakness or cramps
  • Enlarged liver
  • Growth retardation

Diagnosis[edit | edit source]

Genetic testing, a tool used in the diagnosis of GSD.

Diagnosis of GSD involves:

  • Blood tests to measure enzyme levels
  • Liver or muscle biopsy
  • Genetic testing

Treatment[edit | edit source]

Treatment depends on the specific type of GSD:

  • Dietary management (e.g., frequent high-carbohydrate meals to prevent hypoglycemia in Type I GSD)
  • Enzyme replacement therapy for certain types like Type II GSD
  • Supportive treatments for symptoms like muscle cramps

External Links[edit | edit source]

Classification



  1. 3.0 3.1 3.2 3.3 Glycogen Metabolism themedicalbiochemistrypage.org
  2. 4.0 4.1 eMedicine Specialties > Glycogen-Storage Disease Type I Author: Karl S Roth. Updated: Aug 31, 2009
  3. The Association for Glycogen Storage Disease > Type I Glycogen Storage Disease Type I GSD Archived 2010-08-03 at the Wayback Machine October 2006.
  4. https://pediatrics.aappublications.org/content/140/Supplement_1/S4
  5. 8.0 8.1
  6. http://mcardlesdisease.org/
  7. eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases > Glycogen-Storage Disease Type VI Author: Lynne Ierardi-Curto, MD, PhD. Updated: Aug 4, 2008
  8. "Rare Disease Database". Orpha.net. Retrieved 2015-09-20.
  9. Reference, Genetics Home. "Phosphoglycerate mutase deficiency". Genetics Home Reference. Retrieved 2019-02-06.
  10. 14.0 14.1 "Glycogenoses".
  11. Malfatti E, Nilsson J, Hedberg-Oldfors C, Hernandez-Lain A, Michel F, Dominguez-Gonzalez C, Viennet G, Akman HO, Kornblum C, Van den Bergh P, Romero NB, Engel AG, DiMauro S, Oldfors A (2014) A new muscle glycogen storage disease associated with glycogenin-1 deficiency. Ann Neurol 76(6):891-898
  12. GLYCOGEN STORAGE DISEASE IXa1; GSD9A1 OMIM - Online Mendelian Inheritance in Man
  13. "Definition: glycogen storage disease type VIII from Online Medical Dictionary".
  14. Ortolano S, Vieitez I et al. Loss of cortical neurons underlies the neuropathology of Lafora disease. Mol Brain 2014;7:7 PMC 3917365
  15. "Glycogen Storage Disease Type I - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 23 March 2017.
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