Glycogen storage disease type V: Difference between revisions

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==Overview==
==Overview==
'''Glycogen storage disease type V''' also known as McArdle's disease is caused by the deficiency of [[myophosphorylase]]. In 1951, Brian McArdle first described [[Glycogen storage disease|glycogen storage]] type V disease. It is  an [[Autosomal recessive|autosomal recessive disorder]] caused by mutation of the gene ''PYGM which is'' located on chromosome 11q13. [[Myophosphorylase]] is the isozyme of phosphorylase specific to muscles. Its deficiency leads to blockage of [[carbohydrate]] metabolic pathways causing accumulation of excess [[glycogen]] in the muscles. Muscles are unable to produce energy from glycogen and may lead to [[rhabdomyolysis]]. Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of their life. There is insufficient evidence to recommend routine screening for glycogen storage disease type V but [[carrier]] [[Screening (medicine)|screening]] of at-risk relatives may be done. Different individuals present uniquely depending on the severity on enzyme activity. Some adults can develop progressive proximal weakness or fixed motor weakness. A "Second-wind phenomenon" can be seen in patients suffering from glycogen storage disease type V. Burgundy-colored urine can be seen after an intense session of exercise due to rhabdomyolysis. On physical examination persistent weakness and muscle wasting may be seen as the patient ages. Laboratory findings may show elevated levels of [[creatine kinase]] levels in almost 90% of patients suffering from glycogen storage disease type V. Forearm exercise test and [[electromyography]] are used to diagnose GSD type V. Treatment includes dietary modification and mild to moderate [[Aerobic exercise|aerobic exercises]] like walking or bicycling.   
'''Glycogen storage disease type V''' also known as McArdle's disease is caused by the deficiency of [[myophosphorylase]]. In 1951, Brian McArdle first described glycogen storage disease type V. It is  an [[Autosomal recessive|autosomal recessive disorder]] caused by [[mutation]] of the gene PYGM which is located on [[chromosome]] 11q13. [[Myophosphorylase]] is the [[isozyme]] of [[phosphorylase]] specific to muscles. Its deficiency leads to blockage of [[carbohydrate]] metabolic pathways causing accumulation of excess [[glycogen]] in the [[muscles]]. [[Muscles]] are unable to produce energy from [[glycogen]] and may lead to [[rhabdomyolysis]]. Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of their life. There is insufficient evidence to recommend routine screening for glycogen storage disease type V but [[carrier]] [[Screening (medicine)|screening]] of at-risk relatives may be done. Different individuals present uniquely depending on the severity of enzyme deficiency. Some adults can develop progressive proximal [[muscle]] weakness or fixed motor weakness. A "Second-wind phenomenon" can be seen in patients suffering from glycogen storage disease type V. Burgundy-colored urine can be seen after an intense session of exercise due to [[rhabdomyolysis]]. On physical examination persistent weakness and [[muscle wasting]] may be seen as the patient ages. Laboratory findings may show elevated levels of [[creatine kinase]] levels in almost 90% of patients suffering from glycogen storage disease type V. Forearm exercise test and [[electromyography]] are used to diagnose GSD type V. Treatment includes dietary modification and mild to moderate [[Aerobic exercise|aerobic exercises]] like walking or bicycling.   


==Historical Perspective==
==Historical Perspective==
* Glycogen storage disease type V was first described by Brian McArdle, a Scottish physician, in 1951.<ref name="pmid24540673">{{cite journal |vauthors=McARDLE B |title=Myopathy due to a defect in muscle glycogen breakdown |journal=Clin Sci |volume=10 |issue=1 |pages=13–35 |year=1951 |pmid=24540673 |doi= |url=}}</ref>
* Glycogen storage disease type V was first described by Brian McArdle, a Scottish physician, in 1951.<ref name="pmid24540673">{{cite journal |vauthors=McARDLE B |title=Myopathy due to a defect in muscle glycogen breakdown |journal=Clin Sci |volume=10 |issue=1 |pages=13–35 |year=1951 |pmid=24540673 |doi= |url=}}</ref>
* In 1993, the first ''PYGM'' pathogenic mutations were described.<ref name="pmid8401511">{{cite journal |vauthors=Bartram C, Edwards RH, Clague J, Beynon RJ |title=McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases |journal=Hum. Mol. Genet. |volume=2 |issue=8 |pages=1291–3 |year=1993 |pmid=8401511 |doi= |url=}}</ref>
* In 1993, the first PYGM pathogenic mutations were described.<ref name="pmid8401511">{{cite journal |vauthors=Bartram C, Edwards RH, Clague J, Beynon RJ |title=McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases |journal=Hum. Mol. Genet. |volume=2 |issue=8 |pages=1291–3 |year=1993 |pmid=8401511 |doi= |url=}}</ref>


==Classification==
==Classification==
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==Pathophysiology==
==Pathophysiology==
* [[Glycogen storage disease]] type V is caused by the deficiency of liver [[myophosphorylase]].  
* [[Glycogen storage disease]] type V is caused by the deficiency of liver [[myophosphorylase]].  
* Normal function of phophorylase is <ref name="pmid25914343">{{cite journal |vauthors=Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T |title=McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene |journal=Hum. Mutat. |volume=36 |issue=7 |pages=669–78 |year=2015 |pmid=25914343 |doi=10.1002/humu.22806 |url=}}</ref>
* Normal function of phophorylase is:<ref name="pmid25914343">{{cite journal |vauthors=Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T |title=McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene |journal=Hum. Mutat. |volume=36 |issue=7 |pages=669–78 |year=2015 |pmid=25914343 |doi=10.1002/humu.22806 |url=}}</ref>
** Maintains the glucose homeostasis.
** Maintains the glucose homeostasis.
** Leads to the degradation of glycogen into [[glucose-1-phosphate]].
** Leads to the degradation of glycogen into [[glucose-1-phosphate]].
** Alpha-1,4-glucoside residues are removed from the outer branches of the [[glycogen]] molecule.   
** Alpha-1,4-glucoside residues are removed from the outer branches of the [[glycogen]] molecule.   
** Degradation is done until glycogen is broken down to branches of approximately 4 glucosyl units.  
** Degradation is done until glycogen is broken down to branches of approximately 4 glucosyl units.  
* 3 isozymes of phosphorylase are found in the muscles, liver, and brain.  
* 3 [[Isozymes]] of [[phosphorylase]] are found in the [[muscles]], [[liver]], and [[brain]].  
* [[Myophosphorylase]] is the isozyme specific to muscles.  
* [[Myophosphorylase]] is the [[isozyme]] specific to [[muscles]].  
* [[Carbohydrate metabolism|Carbohydrate metabolic pathways]] are blocked which lead to accumulation of excess [[glycogen]] in muscles.
* [[Carbohydrate metabolism|Carbohydrate metabolic pathways]] are blocked which lead to accumulation of excess [[glycogen]] in [[muscles]].
* Muscles are unable to produce energy from glycogen due to deficiency of this enzyme.  
* [[Muscles]] are unable to produce energy from [[glycogen]] due to deficiency of this [[enzyme]].  
* There is an increase in the cellular mechanical stress due to:  
* There is an increase in the [[cellular]] mechanical stress due to:  
** Accumulation of [[glycogen]].
** Accumulation of [[glycogen]].
** Downregulation of [[sodium]]-[[potassium]] pumps.
** Downregulation of [[sodium]]-[[potassium]] pumps.
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* Glycogen storage disease type V is an [[Autosomal recessive|autosomal recessive disorder]].  
* Glycogen storage disease type V is an [[Autosomal recessive|autosomal recessive disorder]].  
* Glycogen storage disease type V is caused by the deficiency of the [[myophosphorylase]] [[enzyme]]. PYGM [[gene mutation]] responsible for the [[myophosphorylase]] [[enzyme]] deficiency is located on [[chromosome]] 11q13.<ref name="pmid259143432">{{cite journal |vauthors=Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T |title=McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene |journal=Hum. Mutat. |volume=36 |issue=7 |pages=669–78 |year=2015 |pmid=25914343 |doi=10.1002/humu.22806 |url=}}</ref>
* Glycogen storage disease type V is caused by the deficiency of the [[myophosphorylase]] [[enzyme]]. PYGM [[gene mutation]] responsible for the [[myophosphorylase]] [[enzyme]] deficiency is located on [[chromosome]] 11q13.<ref name="pmid259143432">{{cite journal |vauthors=Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T |title=McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene |journal=Hum. Mutat. |volume=36 |issue=7 |pages=669–78 |year=2015 |pmid=25914343 |doi=10.1002/humu.22806 |url=}}</ref>
* Disease severity can be  correlated with the genotype at the [[angiotensin-converting enzyme]] (ACE) locus.  
* Disease severity can be  correlated with the [[genotype]] at the [[angiotensin-converting enzyme]] (ACE) locus.  


==Differentiating {{PAGENAME}} from Other Diseases==
==Differentiating {{PAGENAME}} from Other Diseases==
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==Epidemiology and Demographics==
==Epidemiology and Demographics==
* The prevalence of glycogen storage disease type V is approximately 0.6 in 100,000 individuals in spanish community.<ref name="pmid22250184">{{cite journal |vauthors=Lucia A, Ruiz JR, Santalla A, Nogales-Gadea G, Rubio JC, García-Consuegra I, Cabello A, Pérez M, Teijeira S, Vieitez I, Navarro C, Arenas J, Martin MA, Andreu AL |title=Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry |journal=J. Neurol. Neurosurg. Psychiatry |volume=83 |issue=3 |pages=322–8 |year=2012 |pmid=22250184 |doi=10.1136/jnnp-2011-301593 |url=}}</ref>
* The [[prevalence]] of glycogen storage disease type V is approximately 0.6 in 100,000 individuals in spanish community.<ref name="pmid22250184">{{cite journal |vauthors=Lucia A, Ruiz JR, Santalla A, Nogales-Gadea G, Rubio JC, García-Consuegra I, Cabello A, Pérez M, Teijeira S, Vieitez I, Navarro C, Arenas J, Martin MA, Andreu AL |title=Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry |journal=J. Neurol. Neurosurg. Psychiatry |volume=83 |issue=3 |pages=322–8 |year=2012 |pmid=22250184 |doi=10.1136/jnnp-2011-301593 |url=}}</ref>


* The prevalence of glycogen storage disease type V is approximately 1 in 100,000 individuals in Texas, USA.<ref name="pmid10891971">{{cite journal |vauthors=Haller RG |title=Treatment of McArdle disease |journal=Arch. Neurol. |volume=57 |issue=7 |pages=923–4 |year=2000 |pmid=10891971 |doi= |url=}}</ref>  
* The [[prevalence]] of glycogen storage disease type V is approximately 1 in 100,000 individuals in Texas, USA.<ref name="pmid10891971">{{cite journal |vauthors=Haller RG |title=Treatment of McArdle disease |journal=Arch. Neurol. |volume=57 |issue=7 |pages=923–4 |year=2000 |pmid=10891971 |doi= |url=}}</ref>  
* Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of life.  
* Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of life.  


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** [[Myoglobinuria]]
** [[Myoglobinuria]]
** [[Acute kidney injury]]
** [[Acute kidney injury]]
* [[Statin]] should be used with caution as they can lead to myopathy in individuals suffering from glycogen storage disease type V.
* [[Statin]] should be used with caution as they can lead to [[myopathy]] in individuals suffering from glycogen storage disease type V.


=== Prognosis ===
=== Prognosis ===
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====Forearm exercise test====
====Forearm exercise test====
* Forearm exercise test is of 2 types:  
* Forearm exercise test is of 2 types:  
** Nonischemic - preferred type.<ref name="pmid12210784">{{cite journal |vauthors=Kazemi-Esfarjani P, Skomorowska E, Jensen TD, Haller RG, Vissing J |title=A nonischemic forearm exercise test for McArdle disease |journal=Ann. Neurol. |volume=52 |issue=2 |pages=153–9 |year=2002 |pmid=12210784 |doi=10.1002/ana.10263 |url=}}</ref>
** Non-[[ischemic]] - preferred type.<ref name="pmid12210784">{{cite journal |vauthors=Kazemi-Esfarjani P, Skomorowska E, Jensen TD, Haller RG, Vissing J |title=A nonischemic forearm exercise test for McArdle disease |journal=Ann. Neurol. |volume=52 |issue=2 |pages=153–9 |year=2002 |pmid=12210784 |doi=10.1002/ana.10263 |url=}}</ref>
** Minimally ischemic<ref name="pmid16924035">{{cite journal |vauthors=Andersen ST, Dunø M, Schwartz M, Vissing J |title=Do carriers of PYGM mutations have symptoms of McArdle disease? |journal=Neurology |volume=67 |issue=4 |pages=716–8 |year=2006 |pmid=16924035 |doi=10.1212/01.wnl.0000230154.79933.d7 |url=}}</ref>
** Minimally [[ischemic]]<ref name="pmid16924035">{{cite journal |vauthors=Andersen ST, Dunø M, Schwartz M, Vissing J |title=Do carriers of PYGM mutations have symptoms of McArdle disease? |journal=Neurology |volume=67 |issue=4 |pages=716–8 |year=2006 |pmid=16924035 |doi=10.1212/01.wnl.0000230154.79933.d7 |url=}}</ref>
* Normal chemical reactions and products of muscle activity are analysed.  
* Normal chemical reactions and products of [[muscle]] activity are analysed.  
* One-second handgrips are performed every other second for one minute (approximately 30 contractions)  
* One-second handgrips are performed every other second for one minute (approximately 30 contractions)  
* Blood samples are taken to check for [[lactate]], [[ammonia]], and [[creatine kinase]] before starting the test and at 1, 2, 4, 6, 10, 20, and 30 minutes after the end of the exercise.
* [[Blood]] samples are taken to check for [[lactate]], [[ammonia]], and [[creatine kinase]] before starting the test and at 1, 2, 4, 6, 10, 20, and 30 minutes after the end of the exercise.
* A flat venous [[lactate]] curve with normal increase in [[ammonia]] is diagnostic of myophosphorylase deficiency.
* A flat venous [[lactate]] curve with normal increase in [[ammonia]] is diagnostic of myophosphorylase deficiency.
* Earlier blood pressure cuff was used instead of handgrips, but it was stopped because it lead to more muscle pain and acute compartment syndrome.
* Earlier blood pressure cuff was used instead of handgrips, but it was stopped because it lead to more [[muscle pain]] and acute [[compartment syndrome]].


==== Electromyography ====
==== Electromyography ====
* [[Electromyography]] of resting muscle are normal.
* [[Electromyography]] of resting [[muscle]] are normal.
* No electrical activity during contracture is diagnostic of myophosphorylase deficiency.  
* No electrical activity during contracture is diagnostic of myophosphorylase deficiency.  


===History and Symptoms===
===History and Symptoms===
* Different individuals present uniquely depending on the severity on enzyme deficiency.
* Different individuals present uniquely depending on the severity on [[enzyme]] deficiency.
* Some adults can develop:  
* Some adults can develop:  
** Progressive proximal weakness.
** Progressive proximal muscle weakness.
** Fixed motor weakness.
** Fixed motor weakness.
*  Second-wind phenomenon:<ref name="pmid19237700">{{cite journal |vauthors=Ørngreen MC, Jeppesen TD, Andersen ST, Taivassalo T, Hauerslev S, Preisler N, Haller RG, van Hall G, Vissing J |title=Fat metabolism during exercise in patients with McArdle disease |journal=Neurology |volume=72 |issue=8 |pages=718–24 |year=2009 |pmid=19237700 |doi=10.1212/01.wnl.0000343002.74480.e4 |url=}}</ref>
*  Second-wind phenomenon:<ref name="pmid19237700">{{cite journal |vauthors=Ørngreen MC, Jeppesen TD, Andersen ST, Taivassalo T, Hauerslev S, Preisler N, Haller RG, van Hall G, Vissing J |title=Fat metabolism during exercise in patients with McArdle disease |journal=Neurology |volume=72 |issue=8 |pages=718–24 |year=2009 |pmid=19237700 |doi=10.1212/01.wnl.0000343002.74480.e4 |url=}}</ref>
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*** Increased number of motor units
*** Increased number of motor units
*** Increased [[cardiac output]]
*** Increased [[cardiac output]]
*** Use of free fatty acids for muscle metabolism
*** Use of [[free fatty acids]] for [[muscle]] metabolism
* Burgundy-colored urine can be seen after an intense session of exercise.  
* Burgundy-colored urine can be seen after an intense session of exercise.  
** This is believed to be due to [[rhabdomyolysis]].   
** This is believed to be due to [[rhabdomyolysis]].   


===Physical Examination===
===Physical Examination===
* Normal muscle strength and reflexes may be seen.
* Normal [[muscle]] strength and [[reflexes]] may be seen.
* Persistent weakness and muscle wasting may be seen as the patient ages.  
* Persistent weakness and [[muscle wasting]] may be seen as the patient ages.  


===Laboratory Findings===
===Laboratory Findings===
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** It is seen in 50% cases after exercise.
** It is seen in 50% cases after exercise.
* Biochemical assay  
* Biochemical assay  
** Phosphorylase reaction is absent.
** [[Phosphorylase]] reaction is absent.


=== Other Diagnostic Studies ===
=== Other Diagnostic Studies ===


==== Muscle Biopsy ====
==== Muscle Biopsy ====
* Muscle biopsy reveals:<ref name="pmid8757045">{{cite journal |vauthors=Felice KJ, Grunnet ML, Sima AA |title=Selective atrophy of type 1 muscle fibers in McArdle's disease |journal=Neurology |volume=47 |issue=2 |pages=581–3 |year=1996 |pmid=8757045 |doi= |url=}}</ref>  
* Muscle [[biopsy]] reveals:<ref name="pmid8757045">{{cite journal |vauthors=Felice KJ, Grunnet ML, Sima AA |title=Selective atrophy of type 1 muscle fibers in McArdle's disease |journal=Neurology |volume=47 |issue=2 |pages=581–3 |year=1996 |pmid=8757045 |doi= |url=}}</ref>  
** Fiber size variability
** Fiber size variability
** Positive subsarcolemmal blebs with periodic acid-Schiff stain
** Positive subsarcolemmal blebs with [[periodic acid-Schiff stain]]
** Intermyofibril vacuoles
** Intermyofibril vacuoles
** Selective atrophy of type 1 muscle fibers may be seen.
** Selective atrophy of type 1 [[muscle fibers]] may be seen.


==Treatment==
==Treatment==
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* '''Exercise'''  
* '''Exercise'''  
** Mild-to-moderate aerobic exercise like walking, bicycling, or stationary cycling, is beneficial.
** Mild-to-moderate aerobic exercise like walking, bicycling, or stationary cycling, is beneficial.
** Helps to improve cardiovascular fitness and increases muscle oxidative capacity.  
** Helps to improve cardiovascular fitness and increases [[muscle]] oxidative capacity.  
** Strenuous aerobic exercise should be avoided.<ref name="pmid16718692">{{cite journal |vauthors=Haller RG, Wyrick P, Taivassalo T, Vissing J |title=Aerobic conditioning: an effective therapy in McArdle's disease |journal=Ann. Neurol. |volume=59 |issue=6 |pages=922–8 |year=2006 |pmid=16718692 |doi=10.1002/ana.20881 |url=}}</ref><ref name="pmid22161416">{{cite journal |vauthors=Quinlivan R, Vissing J, Hilton-Jones D, Buckley J |title=Physical training for McArdle disease |journal=Cochrane Database Syst Rev |volume= |issue=12 |pages=CD007931 |year=2011 |pmid=22161416 |doi=10.1002/14651858.CD007931.pub2 |url=}}</ref>
** Strenuous aerobic exercise should be avoided.<ref name="pmid16718692">{{cite journal |vauthors=Haller RG, Wyrick P, Taivassalo T, Vissing J |title=Aerobic conditioning: an effective therapy in McArdle's disease |journal=Ann. Neurol. |volume=59 |issue=6 |pages=922–8 |year=2006 |pmid=16718692 |doi=10.1002/ana.20881 |url=}}</ref><ref name="pmid22161416">{{cite journal |vauthors=Quinlivan R, Vissing J, Hilton-Jones D, Buckley J |title=Physical training for McArdle disease |journal=Cochrane Database Syst Rev |volume= |issue=12 |pages=CD007931 |year=2011 |pmid=22161416 |doi=10.1002/14651858.CD007931.pub2 |url=}}</ref>


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[[Category:Endocrinology]]
[[Category:Endocrinology]]
[[Category:Hepatology]]
[[Category:Gastroenterology]]
[[Category:Pediatrics]]
[[Category:Up-To-Date]]
[[Category:Genetic disorders]]
[[Category:Metabolic disorders]]


[[de:Morbus McArdle]]
[[de:Morbus McArdle]]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]

Glycogen storage disease type V
ICD-10 E74.0
ICD-9 271.0
OMIM 232600
DiseasesDB 5307
eMedicine med/911 
MeSH D006012

Overview

Glycogen storage disease type V also known as McArdle's disease is caused by the deficiency of myophosphorylase. In 1951, Brian McArdle first described glycogen storage disease type V. It is an autosomal recessive disorder caused by mutation of the gene PYGM which is located on chromosome 11q13. Myophosphorylase is the isozyme of phosphorylase specific to muscles. Its deficiency leads to blockage of carbohydrate metabolic pathways causing accumulation of excess glycogen in the muscles. Muscles are unable to produce energy from glycogen and may lead to rhabdomyolysis. Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of their life. There is insufficient evidence to recommend routine screening for glycogen storage disease type V but carrier screening of at-risk relatives may be done. Different individuals present uniquely depending on the severity of enzyme deficiency. Some adults can develop progressive proximal muscle weakness or fixed motor weakness. A "Second-wind phenomenon" can be seen in patients suffering from glycogen storage disease type V. Burgundy-colored urine can be seen after an intense session of exercise due to rhabdomyolysis. On physical examination persistent weakness and muscle wasting may be seen as the patient ages. Laboratory findings may show elevated levels of creatine kinase levels in almost 90% of patients suffering from glycogen storage disease type V. Forearm exercise test and electromyography are used to diagnose GSD type V. Treatment includes dietary modification and mild to moderate aerobic exercises like walking or bicycling.

Historical Perspective

  • Glycogen storage disease type V was first described by Brian McArdle, a Scottish physician, in 1951.[1]
  • In 1993, the first PYGM pathogenic mutations were described.[2]

Classification

There is no established system for the classification of glycogen storage disease type V.

Pathophysiology

Causes

Differentiating Glycogen storage disease type V from Other Diseases

Glycogen storage disease Enzyme deficiency Genetics History and symptoms Physical examination Laboratory findings Imaging Other features
Gene mutation Inheritance Chromosome Hypoglycemia Muscle weakness Hypotonia Hepatomegaly Elevated CK Cardiomegaly
Glycogen storage disease type I Von Gierke's disease GSD type Ia Glucose-6-phosphatase G6PC gene mutation  Autosomal recessive 17q21 + + + + - -
  • Lactic acidosis
  • Hyperlipidemia
  • Hyperuricemia
GSD type Ib  Microsomal glucose-6-phosphate transporter  SLC37A4 gene mutation Autosomal recessive 11q23
Glycogen storage disease type II Pompe disease Infantile onset Alpha acid-glucosidase GAA gene Autosomal recessive 17q25 - + + + + +
  • Elevated LDH
  • Elevated liver aminotransferases
  • Elevated urinary glc4
Late onset Autosomal recessive - + + + + +/-
Glycogen storage disease type III Cori disease GSD type IIIa Debranching enzyme (deficiency in muscle and liver) AGL gene mutation  Autosomal recessive 1p21 + + - + + +
  • Ketosis
  • Hyperlipidemia
  • Elevated liver aminotransferases
GSD type IIIb Debranching enzyme (deficiency in liver only) Autosomal recessive
Glycogen storage disease type IV Andersen's disease Branching enzyme  GBE1 gene mutation Autosomal recessive 3p12 + + - + + + -
Glycogen storage disease type V McArdle disease Muscle glycogen phosphorylase PYGM gene mutation Autosomal recessive 11q13 - + - - + -
  • Myoglobuminuria, may result in renal failure
Glycogen storage disease type VI Hers' disease Autosomal Liver glycogen phosphorylase  PYGL gene mutation Autosomal recessive 14q22 +/- + +/- + - -
  • Hyperlipidemia
  • Elevated liver aminotransferases
X-linked X-linked recessive
Glycogen storage disease type VII Tauri's disease Muscle phosphofruktokinase PFKM gene mutation Autosomal recessive 12q13 + + - - + +
Glycogen storage disease type IX GSD type IXa Phosphorylase b kinase (deficiency in liver only) PHKA2 gene mutation X-linked recessive Xp22 + - - + - -
  • Hyperlipidemia
  • Elevated liver aminotransferases
  • Hyperuricemia
  • Fasting ketosis
GSD type IXb Phosphorylase b kinase (deficiency in liver and muscle) PHKB gene mutation Autosomal recessive 16q12 + - - + - -
  • Hyperlipidemia
  • Elevated liver aminotransferases
Glycogen storage disease type X Phosphoglycerate mutase PGAM2 gene mutation Autosomal recessive 7p13 - - - - + -
  • Myoglobinuria
  • Gout (tophy)
  • Severe coronary arteriosclerosis
Glycogen storage disease type XI Lactate dehydrogenase A deficiency LDH A deficiency LDHA gene mutation Autosomal recessive 11p15 - - - - + -
  • Muscle stiffness
  • Lactic acidosis
  • Myoglobinuria
  • Easy fatigue
Glycogen storage disease type XII Aldolase A deficiency Aldolase A ALDOA gene mutation Autosomal recessive 16p11 - + - + - -
  • Hemolytic anemia
  • Splenomegaly
Glycogen storage disease type XIII Beta-enolase  ENO3 gene mutation Autosomal recessive 17p13 - + - - + - -
Glycogen storage disease type XIV Phosphoglucomutase type 2 PGM1 gene mutation Autosomal recessive 1p31 +/- + - - + -
  • Elevated liver aminotransferases
Glycogen storage disease type 0 Lewis' disease Hepatic glycogen synthase  GYS1 gene mutation (muscle)

GYS2 gene mutation (liver)

Autosomal recessive 12p12 + - - - - -
  • Fasting hypoglycemia and ketosis
  • Postprandial hyperglycemia and lactic acidosis

Epidemiology and Demographics

  • The prevalence of glycogen storage disease type V is approximately 0.6 in 100,000 individuals in spanish community.[6]
  • The prevalence of glycogen storage disease type V is approximately 1 in 100,000 individuals in Texas, USA.[7]
  • Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of life.

Risk Factors

  • The most potent risk factor in the development of glycogen storage disease type V is a sibling with glycogen storage disease type V.

Screening

  • There is insufficient evidence to recommend routine screening for glycogen storage disease type V.

Natural History, Complications, and Prognosis

Complications

Prognosis

  • Glycogen storage disease type V is a chronic disorder.

Diagnosis

Diagnostic Study of Choice

Forearm exercise test

  • Forearm exercise test is of 2 types:
  • Normal chemical reactions and products of muscle activity are analysed.
  • One-second handgrips are performed every other second for one minute (approximately 30 contractions)
  • Blood samples are taken to check for lactate, ammonia, and creatine kinase before starting the test and at 1, 2, 4, 6, 10, 20, and 30 minutes after the end of the exercise.
  • A flat venous lactate curve with normal increase in ammonia is diagnostic of myophosphorylase deficiency.
  • Earlier blood pressure cuff was used instead of handgrips, but it was stopped because it lead to more muscle pain and acute compartment syndrome.

Electromyography

  • Electromyography of resting muscle are normal.
  • No electrical activity during contracture is diagnostic of myophosphorylase deficiency.

History and Symptoms

  • Different individuals present uniquely depending on the severity on enzyme deficiency.
  • Some adults can develop:
    • Progressive proximal muscle weakness.
    • Fixed motor weakness.
  •  Second-wind phenomenon:[11]
    • When a patient nearing fatigue slows down the intensity of exercise to a certain level, it can be increased again without recurrence of symptoms.[12]
    • This phenomenon may be due to recruitment of: [13]
  • Burgundy-colored urine can be seen after an intense session of exercise.

Physical Examination

Laboratory Findings

  • Creatine kinase levels are checked in all cases with suspicion of glycogen storage disease.
    • 90% patients suffering from glycogen storage disease type V have elevated levels.
  •  Fasting glucose testing is done to rule out hypoglycemia.
  • Myoglobinuria
    • Urine analysis is done to check for it.
    • It is seen in 50% cases after exercise.
  • Biochemical assay

Other Diagnostic Studies

Muscle Biopsy

Treatment

Medical Therapy

  • Dietary modification
  • Exercise
    • Mild-to-moderate aerobic exercise like walking, bicycling, or stationary cycling, is beneficial.
    • Helps to improve cardiovascular fitness and increases muscle oxidative capacity.
    • Strenuous aerobic exercise should be avoided.[16][17]

Surgery

  • Surgical intervention is not recommended for the management of glycogen storage disease type V.

Primary Prevention

External links


References

  1. ↑ McARDLE B (1951). "Myopathy due to a defect in muscle glycogen breakdown". Clin Sci. 10 (1): 13–35. PMID 24540673.
  2. ↑ Bartram C, Edwards RH, Clague J, Beynon RJ (1993). "McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases". Hum. Mol. Genet. 2 (8): 1291–3. PMID 8401511.
  3. ↑ Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T (2015). "McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene". Hum. Mutat. 36 (7): 669–78. doi:10.1002/humu.22806. PMID 25914343.
  4. ↑ Nogales-Gadea G, Santalla A, Brull A, de Luna N, Lucia A, Pinós T (2015). "The pathogenomics of McArdle disease--genes, enzymes, models, and therapeutic implications". J. Inherit. Metab. Dis. 38 (2): 221–30. doi:10.1007/s10545-014-9743-2. PMID 25053163.
  5. ↑ Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T (2015). "McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene". Hum. Mutat. 36 (7): 669–78. doi:10.1002/humu.22806. PMID 25914343.
  6. ↑ Lucia A, Ruiz JR, Santalla A, Nogales-Gadea G, Rubio JC, García-Consuegra I, Cabello A, Pérez M, Teijeira S, Vieitez I, Navarro C, Arenas J, Martin MA, Andreu AL (2012). "Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry". J. Neurol. Neurosurg. Psychiatry. 83 (3): 322–8. doi:10.1136/jnnp-2011-301593. PMID 22250184.
  7. ↑ Haller RG (2000). "Treatment of McArdle disease". Arch. Neurol. 57 (7): 923–4. PMID 10891971.
  8. ↑ Bollig G (2013). "McArdle's disease (glycogen storage disease type V) and anesthesia--a case report and review of the literature". Paediatr Anaesth. 23 (9): 817–23. doi:10.1111/pan.12164. PMID 23565573.
  9. ↑ Kazemi-Esfarjani P, Skomorowska E, Jensen TD, Haller RG, Vissing J (2002). "A nonischemic forearm exercise test for McArdle disease". Ann. Neurol. 52 (2): 153–9. doi:10.1002/ana.10263. PMID 12210784.
  10. ↑ Andersen ST, Dunø M, Schwartz M, Vissing J (2006). "Do carriers of PYGM mutations have symptoms of McArdle disease?". Neurology. 67 (4): 716–8. doi:10.1212/01.wnl.0000230154.79933.d7. PMID 16924035.
  11. ↑ Ørngreen MC, Jeppesen TD, Andersen ST, Taivassalo T, Hauerslev S, Preisler N, Haller RG, van Hall G, Vissing J (2009). "Fat metabolism during exercise in patients with McArdle disease". Neurology. 72 (8): 718–24. doi:10.1212/01.wnl.0000343002.74480.e4. PMID 19237700.
  12. ↑ Kitaoka Y (2014). "McArdle Disease and Exercise Physiology". Biology (Basel). 3 (1): 157–66. doi:10.3390/biology3010157. PMC 4009758. PMID 24833339.
  13. ↑ Braakhekke JP, de Bruin MI, Stegeman DF, Wevers RA, Binkhorst RA, Joosten EM (1986). "The second wind phenomenon in McArdle's disease". Brain. 109 ( Pt 6): 1087–101. PMID 3466659.
  14. ↑ Felice KJ, Grunnet ML, Sima AA (1996). "Selective atrophy of type 1 muscle fibers in McArdle's disease". Neurology. 47 (2): 581–3. PMID 8757045.
  15. ↑ Vorgerd M, Grehl T, Jager M, Muller K, Freitag G, Patzold T, Bruns N, Fabian K, Tegenthoff M, Mortier W, Luttmann A, Zange J, Malin JP (2000). "Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial". Arch. Neurol. 57 (7): 956–63. PMID 10891977.
  16. ↑ Haller RG, Wyrick P, Taivassalo T, Vissing J (2006). "Aerobic conditioning: an effective therapy in McArdle's disease". Ann. Neurol. 59 (6): 922–8. doi:10.1002/ana.20881. PMID 16718692.
  17. ↑ Quinlivan R, Vissing J, Hilton-Jones D, Buckley J (2011). "Physical training for McArdle disease". Cochrane Database Syst Rev (12): CD007931. doi:10.1002/14651858.CD007931.pub2. PMID 22161416.

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