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Glycogen storage disease, type V(GSD5)

MedGen UID:
5341
Concept ID:
C0017924
Disease or Syndrome
Synonyms: Glycogen storage disease type 5; GSD 5; GSD5; McArdle disease; McArdle type glycogen storage disease; Muscle glycogen phosphorylase deficiency; Myophosphorylase deficiency
SNOMED CT: Glycogen storage disease type 5 (55912009); Glycogenosis, type 5 (55912009); McArdle disease (55912009); Glycogen storage disease type V (55912009); Glycogen storage disease, type V (55912009); Myophosphorylase deficiency glycogenosis (55912009); McArdle's disease (55912009); GSD V (55912009); Muscle glycogen phosphorylase deficiency (55912009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): PYGM (11q13.1)
 
Monarch Initiative: MONDO:0009293
OMIM®: 232600
Orphanet: ORPHA368

Disease characteristics

Excerpted from the GeneReview: Glycogen Storage Disease Type V
Glycogen storage disease type V (GSDV, McArdle disease) is a metabolic myopathy characterized by exercise intolerance manifested by rapid fatigue, myalgia, and cramps in exercising muscles. Symptoms are usually precipitated by isometric exercise or sustained aerobic exercise. Most individuals improve their exercise tolerance by exploiting the "second-wind" phenomenon with relief of myalgia and fatigue after a few minutes of rest. Age of onset is frequently in the first decade of life but can vary; however, diagnosis is typically delayed as myalgia and fatigability are dismissed/overlooked. Fixed muscle weakness occurs in approximately 25% of affected individuals, is more likely to involve proximal muscles, and is more common in individuals of advanced age. Approximately 50% of affected individuals have recurrent episodes of myoglobinuria that can – on occasion – eventually result in acute renal failure. [from GeneReviews]
Authors:
Miguel A Martín  |  Alejandro Lucia  |  Joaquin Arenas, et. al.   view full author information

Additional descriptions

From OMIM
McArdle disease is an autosomal recessive metabolic disorder characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria (summary by Chen, 2001).  http://www.omim.org/entry/232600
From MedlinePlus Genetics
Glycogen storage disease type V (also known as GSDV or McArdle disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells.

People with GSDV typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise (exercise intolerance). Exercise such as weight lifting or jogging usually triggers these symptoms in affected individuals. The discomfort is generally alleviated with rest. If individuals rest after brief exercise and wait for their pain to go away, they can usually resume exercising with little or no discomfort (a characteristic phenomenon known as "second wind").

Prolonged or intense exercise can cause muscle damage in people with GSDV. About half of people with GSDV experience breakdown of muscle tissue (rhabdomyolysis). In severe episodes, the destruction of muscle tissue releases a protein called myoglobin, which is filtered through the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, and it is estimated that half of those individuals with GSDV who have myoglobinuria will develop life-threatening kidney failure.

The signs and symptoms of GSDV can vary significantly in affected individuals. The features of this condition typically begin in a person's teens or twenties, but they can appear anytime from infancy to adulthood. In most people with GSDV, the muscle weakness worsens over time; however, in about one-third of affected individuals, the muscle weakness is stable. Some people with GSDV experience mild symptoms such as poor stamina; others do not experience any symptoms.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-v

Clinical features

From HPO
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Hereditary myoglobinuria
MedGen UID:
44557
Concept ID:
C0027080
Finding
Presence of myoglobin in the urine.
Dark urine
MedGen UID:
604849
Concept ID:
C0426396
Finding
An abnormal dark color of the urine.
Failure to elevate ammonia on ischemic exercise
MedGen UID:
1052425
Concept ID:
CN377129
Finding
Normal subjects display an increase in the concentration of ammonia in the blood following an ischemic exercise test. This term refers to an increase in ammonia that is below the lower limit of normal.
Rhabdomyolysis
MedGen UID:
19775
Concept ID:
C0035410
Pathologic Function
Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Exercise-induced muscle cramps
MedGen UID:
383715
Concept ID:
C1855578
Finding
Sudden and involuntary contractions of one or more muscles brought on by physical exertion.
Exercise-induced rhabdomyolysis
MedGen UID:
867168
Concept ID:
C4021526
Finding
Rhabdomyolysis induced by exercise.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.
Reduced muscle glycogen phosphorylase activity
MedGen UID:
1054027
Concept ID:
CN376954
Finding
Activity of the enzyme glycogen phosphorylase in muscle tissue is below the lower limit of normal. Glycogen phosphorylase (EC 2.4.1.1) is also known as amylophosphorylase, muscle phosphorylase a and b, polyphosphorylase, and myophosphorylase.
Failure to elevate lactate upon ischemic exercise test
MedGen UID:
1052381
Concept ID:
CN377357
Finding
Failure to elevate lactate in blood washed out from ischemically exercised muscles as assayed by the forearm ischemic exercise test.

Professional guidelines

PubMed

Taylor RL, Davis M, Turner E, Brull A, Pinos T, Cabrera M, Nowak KJ
Eur J Hum Genet 2018 May;26(5):758-764. Epub 2018 Jan 25 doi: 10.1038/s41431-017-0070-6. PMID: 29371640Free PMC Article
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5. PMID: 25391139Free PMC Article
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2010 Dec 8;(12):CD003458. doi: 10.1002/14651858.CD003458.pub4. PMID: 21154353

Recent clinical studies

Etiology

Henning F, Cunninghame CA, Martín MA, Rubio JC, Arenas J, Lucia A, HernáNdez-Laín A, Kohn TA
Muscle Nerve 2017 Jun;55(6):916-918. Epub 2016 Dec 16 doi: 10.1002/mus.25472. PMID: 27859426
Michelle EH, Mammen AL
Curr Rheumatol Rep 2015 Oct;17(10):63. doi: 10.1007/s11926-015-0541-0. PMID: 26290112
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5. PMID: 25391139Free PMC Article
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2010 Dec 8;(12):CD003458. doi: 10.1002/14651858.CD003458.pub4. PMID: 21154353
Quinlivan R, Beynon RJ, Martinuzzi A
Cochrane Database Syst Rev 2008 Apr 16;(2):CD003458. doi: 10.1002/14651858.CD003458.pub3. PMID: 18425888

Diagnosis

Urtizberea JA, Severa G, Malfatti E
Genes (Basel) 2023 Apr 22;14(5) doi: 10.3390/genes14050954. PMID: 37239314Free PMC Article
Gooch C, Dean SJ, Marzullo L
Pediatr Emerg Care 2021 Dec 1;37(12):e1759-e1760. doi: 10.1097/PEC.0000000000002079. PMID: 32205805
Tarnopolsky MA
Continuum (Minneap Minn) 2016 Dec;22(6, Muscle and Neuromuscular Junction Disorders):1829-1851. doi: 10.1212/CON.0000000000000403. PMID: 27922496
Nogales-Gadea G, Godfrey R, Santalla A, Coll-Cantí J, Pintos-Morell G, Pinós T, Arenas J, Martín MA, Lucia A
Physiol Genomics 2016 Feb;48(2):93-100. Epub 2015 Oct 13 doi: 10.1152/physiolgenomics.00076.2015. PMID: 26465709
Michelle EH, Mammen AL
Curr Rheumatol Rep 2015 Oct;17(10):63. doi: 10.1007/s11926-015-0541-0. PMID: 26290112

Therapy

Üsküdar Cansu D, Erdoğan B, Korkmaz C
Clin Rheumatol 2019 Oct;38(10):2941-2948. Epub 2019 May 1 doi: 10.1007/s10067-019-04572-8. PMID: 31044384
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5. PMID: 25391139Free PMC Article
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2010 Dec 8;(12):CD003458. doi: 10.1002/14651858.CD003458.pub4. PMID: 21154353
Quinlivan R, Beynon RJ, Martinuzzi A
Cochrane Database Syst Rev 2008 Apr 16;(2):CD003458. doi: 10.1002/14651858.CD003458.pub3. PMID: 18425888
Quinlivan R, Beynon RJ
Cochrane Database Syst Rev 2004;(3):CD003458. doi: 10.1002/14651858.CD003458.pub2. PMID: 15266486

Prognosis

Urtizberea JA, Severa G, Malfatti E
Genes (Basel) 2023 Apr 22;14(5) doi: 10.3390/genes14050954. PMID: 37239314Free PMC Article
Carvalho AAS, Christofolini DM, Perez MM, Alves BCA, Rodart I, Figueiredo FWS, Turke KC, Feder D, Junior MCF, Nucci AM, Fonseca FLA
PLoS One 2020;15(7):e0236597. Epub 2020 Jul 31 doi: 10.1371/journal.pone.0236597. PMID: 32735634Free PMC Article
Üsküdar Cansu D, Erdoğan B, Korkmaz C
Clin Rheumatol 2019 Oct;38(10):2941-2948. Epub 2019 May 1 doi: 10.1007/s10067-019-04572-8. PMID: 31044384
Rodríguez-Gómez I, Santalla A, Díez-Bermejo J, Munguía-Izquierdo D, Alegre LM, Nogales-Gadea G, Arenas J, Martín MA, Lucía A, Ara I
J Inherit Metab Dis 2018 Nov;41(6):1037-1042. Epub 2018 Mar 28 doi: 10.1007/s10545-018-0170-7. PMID: 29594644
Taylor RL, Davis M, Turner E, Brull A, Pinos T, Cabrera M, Nowak KJ
Eur J Hum Genet 2018 May;26(5):758-764. Epub 2018 Jan 25 doi: 10.1038/s41431-017-0070-6. PMID: 29371640Free PMC Article

Clinical prediction guides

Carvalho AAS, Christofolini DM, Perez MM, Alves BCA, Rodart I, Figueiredo FWS, Turke KC, Feder D, Junior MCF, Nucci AM, Fonseca FLA
PLoS One 2020;15(7):e0236597. Epub 2020 Jul 31 doi: 10.1371/journal.pone.0236597. PMID: 32735634Free PMC Article
Üsküdar Cansu D, Erdoğan B, Korkmaz C
Clin Rheumatol 2019 Oct;38(10):2941-2948. Epub 2019 May 1 doi: 10.1007/s10067-019-04572-8. PMID: 31044384
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5. PMID: 25391139Free PMC Article
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2010 Dec 8;(12):CD003458. doi: 10.1002/14651858.CD003458.pub4. PMID: 21154353
Quinlivan R, Beynon RJ, Martinuzzi A
Cochrane Database Syst Rev 2008 Apr 16;(2):CD003458. doi: 10.1002/14651858.CD003458.pub3. PMID: 18425888

Recent systematic reviews

Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5. PMID: 25391139Free PMC Article
Quinlivan R, Vissing J, Hilton-Jones D, Buckley J
Cochrane Database Syst Rev 2011 Dec 7;(12):CD007931. doi: 10.1002/14651858.CD007931.pub2. PMID: 22161416
Quinlivan R, Martinuzzi A, Schoser B
Cochrane Database Syst Rev 2010 Dec 8;(12):CD003458. doi: 10.1002/14651858.CD003458.pub4. PMID: 21154353
Quinlivan R, Beynon RJ, Martinuzzi A
Cochrane Database Syst Rev 2008 Apr 16;(2):CD003458. doi: 10.1002/14651858.CD003458.pub3. PMID: 18425888
Quinlivan R, Beynon RJ
Cochrane Database Syst Rev 2004;(3):CD003458. doi: 10.1002/14651858.CD003458.pub2. PMID: 15266486

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