McArdle's Disease: Difference between revisions

No edit summary
(Removed copyright violation image)
 
(129 intermediate revisions by 7 users not shown)
Line 1: Line 1:
<nowiki><nowiki>Insert non-formatted text here</nowiki>&lt;/nowiki&gt;&nbsp;
<div class="editorbox">'''Original Editors '''- [[User:Edward Foring|Ed Foring]]&nbsp;as part of [[Pathophysiology of Complex Patient Problems|Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  
<div class="noeditbox">Welcome to [[Pathophysiology of Complex Patient Problems|PT 635 Pathophysiology of Complex Patient Problems]] This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!</div><div class="editorbox">
'''Original Editors '''- [[User:Edward Foring|Ed Foring]]&nbsp;as part of [[Pathophysiology of Complex Patient Problems|Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  


'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp; [[Physiopedia:Editors|Read more.]]
'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;
</div>  
</div>  
&nbsp;


== Definition/Description<br>  ==
== Definition/Description ==
[[File:Chromosome-DNA-gene copy.jpg|right|frameless]]
McArdle disease is a [[Genetic Conditions and Inheritance|genetic disorder]] that mainly affects [[Muscle Cells (Myocyte)|skeletal muscles]]. It occurs due to the deficiency or absence of an [[Enzymes|enzyme]] called myophosphorylase, a key substance that the [[Muscle|muscles]] need to break down [[glycogen]] into sugar (glucose) for energy. Symptoms include painful [[Exercise-Associated Muscle Cramps|muscle cramps]], weakness, and fatigue manifested during periods of [[Physical Activity|physical activity]].<ref name=":0">Khattak ZE, Ashraf M. [https://www.statpearls.com/articlelibrary/viewarticle/24796/ McArdle Disease.] StatPearls [Internet]. 2020 Aug 15. Available:https://www.statpearls.com/articlelibrary/viewarticle/24796/ (accessed 23.10.2021)</ref> The disease can lead to dark [[urine]].  


McArdle’s Disease, also referred to as Myophosphorylase Deficiency, or Type V Glycogen Storage Disease, was first described in 1951 by Dr. Brian McArdle while he was practicing in London, England. The condition is a recessive inherited disorder that presents as an inability to metabolize glycogen, the storage form of glucose. This results in a variety of symptoms affecting the musculoskeletal and urinary systems. Patients afflicted by McArdle’s Disease most commonly suffer from muscle fatigue.  
* Severe, uncontrolled McArdle disease can cause life-threatening [[kidney]] problems.<ref name=":1">Cedars Sinai [https://www.cedars-sinai.org/health-library/diseases-and-conditions/m/mcardle-disease.html McArdle Disease] Available: https://www.cedars-sinai.org/health-library/diseases-and-conditions/m/mcardle-disease.html (accessed 23.10.2021)</ref>
* To avoid the unpleasant symptoms associated with this condition and improve the [[Quality of Life|quality of life]], the disease requires prompt diagnosis and treatment.<ref name=":0" />


Refer to the model below to see how muscle contraction differs in an unaffected muscle compared to one with McArdle’s Disease.  
== Etiology ==
McArdle disease typically results from mutations involving the muscle-specific isoform of the glycogen phosphorylase enzyme. This enzyme plays a key role in the first step of [[Glycolysis|glycogenolysis]] that release glucose-1-phosphate monomers in muscle fibers. As a result, [[Carbohydrates|carbohydrate]] metabolism of the skeletal-muscle is affected, and energy cannot be generated from the glycogen stores of muscles.


<br>  
Image 2:How muscle contraction differs in an unaffected muscle compared to one with McArdle’s Disease.<br>  


{| style="width: 698px; height: 388px" cellspacing="1" cellpadding="1" width="698" border="1"
[[Image:Screen Shot 2017-04-04 at 10.14.25 PM.png|center|771x771px|alt=]]<ref name="p1">MedPoster 1992. nobelprize.org. [cited 3 April 2011]. Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/1992/illpres/glycogen.html</ref><ref name="p2">McArdlesDisease.org. [cited 17 March 2011]. Available from: www.mcardledisease.org</ref>
|-
| '''How Skeletal Muscle Normally Contract'''
| '''A McArdle's Diease Model'''
|-
| [[Image:Glycogen-metabolism.gif|left|1. Acetylcholine is released from a motor nerve. This causes an entry of calcium into the muscle cell.]]
| [[Image:Energy 2.gif|Image:Energy_2.gif]]
|}


<br>  
== Epidemiology ==
The exact prevalence of McArdle disease is not precisely known and appears to range from 1 in 50,000 to 1 in 200,000 in the United States. <ref name=":0" />


{| style="width: 708px; height: 381px" cellspacing="1" cellpadding="1" width="708" border="1"
== Characteristics/Clinical Presentation ==
|-
McArdle Disease patients can have critical episodes of early fatigue when exercising, muscle pain (myalgia), myoglobinuria (when muscles break down and release myoglobin in urine, making it brown/red in colour), and then subsequent kidney failure<ref name=":2">Brain Foundation McArdle Disease Award - 2012 Available: https://brainfoundation.org.au/research-grants/2012/mcardle-disease-award/ (accessed 23.10.2021)</ref>. Some common symptoms of McArdle disease are:
|
<sub>1. </sub>Acetylcholine is released from a motor nerve. This causes an entry of calcium into the muscle cell.


|
* Better able to do aerobic exercise after 8 to 10 minutes (second-wind phenomenon)
1. Acetylcholine is released from a motor nerve. This causes an entry of calcium into the muscle cell.  
* Brownish red urine, especially after periods of activity
* Easily tiring during activity, with stiffness or weakness soon after starting exercise
* Muscle cramping
* Muscle pain
* Lasting (permanent) weakness in the thigh or other muscles. This happens in a small portion of people with the condition.


|-
Most of the time, people notice these symptoms before age 15. Often, people assume the symptoms are “growing pains” or due to some other cause. Different people may have symptoms of different severity eg person noticing that the symptoms seem worse or better at different times.<ref name=":1" />
|
2. Calcium activates phosphorylase kinase – the first protein kinase discovered by Fischer and Krebs.  


|
== Diagnosis ==
2. Calcium activates phosphorylase kinase – the first protein kinase discovered by Fischer and Krebs.
Some diagnostic tests include:


|-
* [[Blood Tests|Blood tests]] to check for muscle enzymes, such as creatine kinase
|  
* DNA blood tests for known McArdle disease mutations
3. Phosphorylase kinase phosphorylates phosphorylase, which is activated
* Electromyography to measure the electrical activity of the muscles
* Forearm exercise test
* [[MRI Scans|MRI]] studies of your muscles
* Muscle biopsy to examine the muscle cells for glycogen buildup
* Urine tests to check for myoglobin, which darkens the urine<ref name=":1" />


|  
== Associated Co-morbidities ==
3. Phosphorylase kinase phosphorylates phosphorylase, which is missing or otherwise non-functional
*[[Chronic Kidney Disease|'''Renal''' '''Failure''']]: Kidney dysfunction and failure are associated with rhadbomyolysis and myoglobinuria.


|-
*'''[[Gout]]''': Inhibited ATP production leads to the production or purine metabolites. These metabolites are converted to uric acid, which can lead to hyperuricemia. <ref name="p1" /><ref name="p2" /><ref>Driver MDCB. Gout Causes, Diet, Symptoms, Treatment &amp; Medication [Internet]. MedicineNet. [cited 2017Apr5]. Available from: http://www.medicinenet.com/gout_gouty_arthritis/article.htm</ref>
|  
== Treatment ==
4. Glycogen is broken to glucose. This is used to generate ATP
[[File:Fish.jpeg|right|frameless]]
Patients with McArdle Disease cannot utilise their glycogen energy stores in their skeletal muscles. Despite a great deal of intensive investigation, no effective treatment for McArdle Disease has been found.<ref name=":2" />


|
Image 3: Creatine rich food, most people get creatine through seafood and red meat (though at levels far below those found in synthetically made creatine supplements)
4. Glycogen is unable to be broken down, creating glucose (and ATP) shortage.


|-
Persons may be able to use certain diet and exercise strategies to help control the problem. A well-designed low or moderate exercise routine may help the body get the most out of its' ability to use glucose. Overdoing exercise can harm the muscles and kidneys in people with McArdle disease. A healthcare team is vital in creating the best care plan for the situation. Some therapies used to help manage McArdle disease are:
|
5. The muscle works and requires energy in the form of ATP


|  
* Careful attention to a diet rich in carbohydrates
5. Motor proteins attach to muscle fibers require ATP for movement.
* [[Creatine and Exercise|Creatine]] supplements
* Eating or drinking prescribed amounts of sucrose before exercise
* Prescribed, moderate aerobic exercise plan
* Other medicines, such as ACE inhibitors


|-
People with McArdle disease need to work with their care team and physio to establish a safe exercise plan.  
|
6. The muscle contains muscle cells


|
There are currently no medications used to treat McArdle's Disease.<ref name=":1" />
6. Muscles stop responding in absence of ATP .  


|-
== Diet ==
|
Certain dietary interventions which confer favorable effects include taking a sugary meal before planning exercise - for example, having a drink containing 75g sucrose 40 minutes before exercise alleviates typical symptoms of exercise intolerance. A diet rich in carbohydrates results in much better outcomes in comparison to a protein-rich diet. Other nutritional agents that were helpful for some patients but could not yield convincing outcomes during actual experimental studies include branched-chain amino acids, depot glucagon preparations, verapamil, dantrolene sodium, vitamin B6, high dose D-ribose, and high-dose creatine ingestion.<ref name=":0" />
7. Contractile proteins in the muscle are activated by calcium


|
== Physical Therapy Management ==
7. Because ATP is required to both contract and relax muscles, injury can occur.  
The physical therapist has an important role in keeping the patient active and avoiding inactivity due to fatigue.'''<br>'''Optimal exercise programs for managing McArdle’s Disease are aerobic based; they provide light resistance along with a [[Aerobic Exercise|cardiovascular]] component.  


|}
*A plan of care incorporating low to moderate intensity [[Aerobic Exercise|aerobic physical activity]] can improve symptoms and reduce susceptibility to injury of the muscle.
*The goal is to achieve the "second wind" for each muscle group that is being worked.
*Light to moderate resistance training can also help, but allow adequate time to rest in between sets.
*As a rule, do not work the muscles to absolute fatigue, and be sure to target larger muscle groups.
*If strenuous activity must be done, use a 6 second rule. Only do that activity for 6 seconds prior to resting to ensure that only the phosphagen energy system is used in [[Anaerobic Exercise|anaerobic activity]].<br>


<ref>MedPoster 1992. nobelprize.org. http://nobelprize.org/nobel_prizes/medicine/laureates/1992/illpres/glycogen.html (accessed 3 April 2011).</ref><ref name="MDORG">McArdlesDisease.org. www.mcardledisease.org (accessed 17 March 2011).</ref><br>
'''Physical therapists can promote flexibility in order to prevent muscle contractures and reduce pain.'''


<br>
*[[Stretching]] should be very light because maximal stretching will work the muscle anaerobically by inducing a protective contraction from the [[Golgi Tendon Organ|Golgi tendon]]. This strong protective contraction can lead to muscle damage.
*Stretching following walking may offer immediate and dramatic pain relief to individuals with McArdle’s Disease.
*For active individuals, stretching should take place very frequently to help reduce cramping. If not, muscles may become tight due to the toxic build up throughout activity and stretching can become painful.
*Physical therapists should encourage a stretch that feels sufficient without causing pain.


= Prevalence  =
'''Physical therapists should promote active participation by patients in managing their disease.'''


*McArdle's Disease is rare and affects approximately 1 in 100,000 people. However, it is one of the most common disorders affecting muscle metabolism.
*Individuals with McArdle’s Disease can easily overexert themselves and become injured without even realizing it.  
*The disease presents more often in men than women.  
*It is important that they be conscious of their energy levels, blood sugar, [[Pulse rate|heart rate]], and general well-being.
*It is believed that many people remain undiagnosed.
*It presents in the second to third decade of life with symptoms reported at childhood.


<br> <ref name="MDORG" /><ref name="mda" />


= Characteristics/Clinical Presentation  =
For a brief discussion of treating a patient with McArdle's Disease, refer to the video below. {{#ev:youtube|qsnDu-fLdRs}}


*The earliest and most common signs and symptoms of McArdle’s Disease are '''exercise''' '''intolerance''' and '''fatiguability'''.
*Other signs and symptoms may include myalgia, muscle contractures, stiffness, cramping, rhabdomyolysis, myoglobinuria, and second wind.
*Symptoms typically present 10 seconds after beginning strenuous exercise. This is when skeletal muscle relies on the conversion of glycogen to glucose to produce ATP, the main energy source for muscular contraction.
*The inability of the skeletal muscles to metabolize glycogen into glucose with strenuous activity leads to an abrupt feeling of exhaustion or fatigue and an increase in heart rate. This is known as '''premature''' '''exhaustion'''. Individuals may complain of difficulty with any moderate activity including walking, jogging, or ascending and descending steps.
*'''Muscle'''&nbsp;'''failure''' occurs under extreme stress when the muscle no longer can produce contraction regardless of the effort made. Muscle failure leads to cramping (electrically silent contractions), which are very painful and can lead to muscle damage.
*The body begins to break down muscle to provide the cells with a tertiary energy source in the form of protein. This process, referred to as '''rhabdomyolysis''', releases creatine kinase and myoglobin into the blood, and excretes those proteins with urination.
*'''Myoglobinuria''' is the symptom that refers to the reddish coloration of urine due to the high protein concentration, ultimately leading to kidney dysfunction and failure.
*Muscle damage caused by rhabdomyolysis can lead to '''fixed''' '''weakness''', or persistent muscle weakness, that makes it extremely difficult to make strength gains.
*“'''Second''' '''Wind'''” is the phenomenon that has been observed in patients with McArdle’s Disease, in which the metabolic pathway switches from glycolytic to oxidative phosphorylation.
*After 10 seconds, all of the readily available glucose in the system is depleted and the patient begins to fatigue.
*From 10 seconds to about 8 minutes of exercise, the patient will experience moderate to severe pain from the muscles breaking down in order to compensate for the inability to breakdown glycogen.
*After 8-10 minutes, the second wind will kick in and the patient should be able to continue exercising for 45 minutes without pain and with an appropriate heart rate response, depending on their level of physical fitness.
*Second wind can be monitored through a patient’s heart rate. After reaching an inappropriate peak, the heart rate will lower and level off, signifying the start of the second wind.
*Second wind is not a systemic effect, and must be achieved in each muscle group independently.
*This does not relieve muscle failure symptoms for intense exercise, but offers some relief for light to moderate exercise.<br>


<br>
<ref name="p5">Reference G. glycogen storage disease type V. Genetics Home Reference. 2017 [cited 18 March 2017]. Available from: https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v</ref><ref name="p0">Olafsen A. Quest - Article - McArdle’s Disease: The Right Diagnosis Can Lighten the Load - A Quest Article | Muscular Dystrophy Association. Muscular Dystrophy Association. 2017 [cited 18 March 2017]. Available from: https://www.mda.org/quest/article/mcardles-disease-diagnosis</ref><ref name="p5" /><ref name="p7">MedScape. [cited 19 April 2011]. Available from: http://www.medscape.org/viewarticle/581307_4</ref><ref>Exercise for Homeschoolers [Internet]. Texas Rock Gym. [cited 2017Apr5]. Available from: http://www.texasrockgym.com/exercise-for-homeschoolers/</ref>  


<span style="font-size: 25px;">Associated Co-morbidities</span>  
== Alternative/Holistic Management ==
[[Massage]]''':''' Individuals with McArdle’s Disease claim that massage therapy can be beneficial in maintaining an active lifestyle. Any massage should be light and fluid using effleurage techniques. Deep and hard massage for trigger point or myofascial release can be damaging to the muscle and should be avoided. Massages help push fatigue causing toxins out of the muscles and into the blood stream where they can be excreted from the body. It is recommended that individuals with McArdle’s Disease take in plenty of fluids following a massage to help flush the body of toxins. Pain with massage is a sign that rhabdomyolysis may be occurring. Do not continue massage therapy with pain.<ref name="p1" /><ref name="p2" /><ref>Home [Internet]. Natural Tranquility Massage and Bodywork LLC. [cited 2017Apr5]. Available from: http://naturaltranquilitymassage.com/</ref>
== Differential Diagnosis ==


*'''Renal''' '''Failure''': Kidney dysfunction and failure are associated with rhadbomyolysis and myoglobinuria.
* [[Rhabdomyolysis]]
*'''Gout''': Inhibited ATP production leads to the production or purine metabolites. These metabolites are converted to uric acid, which can lead to hyperuricemia. The most common place for gout to form is the first metatarsal; however it can be found in the insteps, ankles, heels, knees, wrist, fingers, and elbows as well.
* [[Fibromyalgia]]
* [[Muscular Dystrophy]]
* [[Myositis Ossificans of the Quadriceps|Myositis]]
* Tarui's Disease: A condition in which there exists a deficiency of the phosphofructokinase enzyme, which is needed to facilitate the breakdown of glucose into energy in muscle during exercise. Tarui’s Disease is also a glycogen storage deficiency, so it has many similarities to McArdle’s Disease. Consequently, they are treated in a similar manner. <ref name="p0" /><ref name="p1" /><ref name="p2" /><ref name="p3">Baechle Thomas R and Roger W Earle. Essentials of Strength Training and Conditioning. Human Kinetics. Champaign,IL 2008.</ref><ref name="p4">McArdle’s Disease (Glycogen Storage Disease Type V). Patient.info. 2017 [cited 18 March 2017]. Available from: http://patient.info/doctor/mcardles-disease-glycogen-storage-disease-type-v</ref>


<ref name="Med">MedScape. http://www.medscape.org/viewarticle/581307_4 (accessed 19 April 2011).</ref>&nbsp;<ref name="NIAMS">NIAMS.http://www.niams.nih.gov/Health_Info/Gout/default.asp (accessed 19 April 2011).</ref>
==Case Study McArdle Disease==
This [[Case Study McArdle Disease|case]] demonstrates some of the day-to-day struggles of living with McArdle's Disease along with associated signs and symptoms of the disease. It also discusses abnormal lab values and possible physical therapy interventions and outcomes


= Medications  =
<ref name="p9">Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). 2017.</ref>


There are currently no medications used to treat McArdle's Disease.<br>
== References ==


= <span style="font-size: 20px;">Supplements</span>  =
Special thank you to Andrew Wakelin, McArdle’s Disease (GSD Type V) Coordinator for AGSD UK for review and insight towards this page.


*'''Vitamin''' '''B6''' (mixed evidence): Izume (2010) found decreased fatigue and increased glycogenolysis as seen on the ischemic forearm test with B6 supplementation. Beynon (1998) found no significant improvements compared to a placebo treatment. However, approximately 80% of vitamin B6 binds to myophyphoralyse, so patients with McArdle’s Disease may need to supplement B6 to avoid deficiency.
<references />
*'''Ramipril''': 2.5 mg orally daily showed some subjective improvement in participants with the D/D ACE polymorphism
[[Category:Conditions]]
*'''Creatine''' '''supplements''': Vorgerd (2000, 2002) found an increase in exercise tolerance of workload and depletion in phosphocreatine with low levels of creatine supplementation, but an increase in symptoms with high levels of creatine supplementation.
[[Category:Paediatrics - Conditions]]
*'''Oral''' '''Sucrose''': Vissing (2003) concluded that oral ingestion of sucrose can significantly improve exercise tolerance in McArdle’s Disease. However, overtime this supplementation may cause weight gain and is contraindicated for any individual with diabetes.
[[Category:Genetic Disorders]]
*There is a lack of evidence to show benefit from supplementation with branched chain amino acids, depot glucagon, dantrolene sodium, verapamil or, high-dose oral ribose. <br><br>
 
== Diet  ==
 
'''Tarnopolsky’s diet recommendations'''
 
*Carbohydrate-rich diet: (20% fat, 15% protein and 65% carbohydrate)
*Anderson (2008) found that this diet, compared to a protein rich diet (55% protein, 30% carbohydrate and 15% fat), resulted in a significant drop in heart rate and work effort with a 25% increase in maximal oxygen uptake.
*A low carbohydrate is not recommended because it will deplete liver glycogen and reduce the amount of glucose released into the blood stream. This will lead to hypoglycemia (low blood sugar) when the person becomes active.
*It is recommended to consume a sugary drink or snack before participating in strenuous activity to provide the body with immediate energy before the second wind is achieved.<br><ref name="mda">McArdle's Disease. www.mda.org (accessed 19 April 2011)</ref>
 
= Diagnostic Tests/Lab Tests/Lab Values  =
 
'''[http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm Creatine Phosphokinase Test]&nbsp;'''
 
If lab work is conducted than the patient will have an elevated CPK test. This alone does not conclude the individual has McArdle's disease because CPK values will be elevated due to any muscle breakdown in the system. When the brain, heart or skeletal muscle has significant damage it releases an enzyme called creatine phosphokinase. In McArdle's disease the inability of glycogen to turn into glucose for energy; the muscle breaks down itself releasing this enzyme into the blood stream.
 
'''Ischemic Forearm Test'''
 
This test is a valuable diagnostic test for a number of metabolic diseases. Speaking generally, the test measures concentration of lactic acid in the blood before and after local exertion of a muscle group. The following protocol description is taken from the [http://www.med.ufl.edu/rheum/rheumTests.htm#ischemic University of Florida School of Medicine website]:
 
''The test is performed by contracting the forearm to fatigue with a blood pressure cuff inflated to greater than systolic pressure. Antecubital blood samples for lactate and ammonia are collected before and following exercise at 0, 1, 2, 5, and 10 minutes. Ischemia blocks oxidative phosphorylation and ensures dependence on anaerobic glycogenolysis lactate normally rises at least fourfold within 1 to 2 minutes of exercise ammonia rises fivefold within 2 to 3 minutes.''
 
''Lactate concetration will rise several-fold under ischemic conditions in normal subjects (o-o-o). There will be no or minimal rise in patients with myophosphorylase deficiency (McArdle’s disease.)''
 
The ischemic forearm test is only&nbsp;slightly uncomfortable to undergo, involving blood samples, a pressure cuff, and a device to squeeze with the hand for forearm muscle contraction, but takes a few hours in order to get blood samples at a resting metabolic rate.
 
<u>'''This test has now been replaced by the non-ischemic forearm test.'''</u>
 
'''Non-Ischemic Forearm Test'''
 
This test is done in the same manor as the ischemic forearm test but without the blood pressure cuff. [http://www.ncbi.nlm.nih.gov/pubmed/12210784 Click here to learn more.]  
 
'''Muscle Biopsy''' <br>The biopsy looks for the presence of myophosphorylase activity, which is absent in and can confirm diagnosis of McArdle’s disease. [http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=912 Click here to view biopsy images of McArdle's Disease.]
 
<br>
 
<ref name="MDORG" /><ref name="medline">Medline Plus. http://www.nlm.nih.gov/medlineplus (accessed 3 April 2011).</ref>&nbsp;<ref name="geneva">Geneva Foundation for Medical Education and Research. Glycogen Storage disease V. http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=912 (accessed 3 April 2011).</ref><ref>University of Florida. Medical Center. http://www.med.ufl.edu/rheum/rheumTests.htm#ischemic (accessed 19 April 2011)</ref> <ref name="pubmed">PubMed. http://www.ncbi.nlm.nih.gov/pubmed (accessed 19 April 2011)</ref>
 
= Etiology/Causes<br> =
 
McArdle’s Disease has been shown to have an autosomal recessive inheritance pattern, requiring two defective copies of the gene for the condition to manifest. The defect exists as mutation of the gene for myophosphorylase (PYGM), which occurs on chromosome 11. Myophosphorylase is an enzyme that helps break down glycogen into glucose during exercise. Carriers of the gene are not known to have symptoms of the disease.
 
= Systemic Involvement  =
 
There has not been any long term studies that have found long term effects on the general health on individuals with McArdle's Diease. Typically individuals with this disease are in excellent health as long as the disease&nbsp;is managed properly. If&nbsp;the disease is unmanaged, resulting in constant cases&nbsp;of rhabdomyolysis, it can lead to kidney and liver dysfunctions.&nbsp;
 
<br>
 
'''Precaution: '''Any patient with&nbsp;McArdle's disease that has cardiovascular complication could be on a statin medication. Statin's increase the potential risk for rhabdomyolysis. Therefore physical activity should be keep to an absolute minimum.
 
<ref name="mda" /><ref name="MDORG" />
 
= Medical Management (current best evidence)  =
 
[http://www.agsd.org.uk/portals/32/attachments/CochranePharmAndNutritional2010.pdf Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD003458. DOI: 10.1002/14651858.CD003458.pub4]<br>
 
<br>
 
= Physical Therapy Management (current best evidence)  =
 
The physical therapist has an important role in keeping the patient active and avoiding inactivity due to fatigue.<br>
 
• Optimal exercise programs for managing McArdle’s Disease are aerobic based; they provide light resistance along with a cardiovascular component.<br>• A plan of care incorporating low to moderate intensity aerobic physical activity can improve symptoms and reduce susceptibility to injury of the muscle.<br> • The goal is to achieve the "second wind" for each muscle group that is being worked. <br>• Light to moderate resistance training can also help, but allow adequate time to rest in between sets.<br>• As a rule, do not work the muscles to absolute fatigue, and be sure to target larger muscle groups.<br>• If strenuous activity must be done use a 6 second rule, only do that activity for 6 seconds prior to resting to ensure that only the phosphagen energy system is used in anaerobic activity.
 
Physical therapists can promote flexibility in order to prevent muscle contractures and reduce pain.
 
• Stretching should be very light because maximal stretching will work the muscle anaerobically by inducing a protective contraction from the Golgi tendon. This strong protective contraction can lead to muscle damage.<br>• Stretching following walking may offer immediate and dramatic pain relief to individuals with McArdle’s Disease. <br>• For active individuals, stretching should take place very frequently to help reduce cramping. If not, muscles may become tight due to the toxic build up throughout activity and stretching can become painful.<br>• Physical therapists should encourage a stretch that feels sufficient without causing pain.
 
<br>Physical therapists should promote active participation by patients in managing their disease.
 
<br>• Individuals with McArdle’s Disease can easily over exert themselves and become injured without even realizing it.<br>• It is important that they be conscious of their energy levels, blood sugar, heart rate, and general well-being.<br>• These individuals have a place in physical therapy to improve aerobic capacity, strength, and flexibility.<br>• During any low to moderate intensity activities, patients with McArdle’s Disease should warm up properly until they achieve the "second wind. Strenuous activities should be limited to six seconds to ensure the use of the phosphagen system.
 
= Alternative/Holistic Management (current best evidence)<br> =
 
'''Massage'''<br>o Individuals with McArdle’s Disease claim that massage therapy can be beneficial in maintaining an active lifestyle. <br>o Any massage should be light and fluid using effleurage techniques. Deep and hard massage for trigger point or myofascial release can be damaging to the muscle and should be avoided.<br>o Massages help push fatigue causing toxins out of the muscles and into the blood stream where they can be excreted from the body. It is recommended that individuals with McArdle’s Disease take in plenty of fluids following a massage to help flush the body of toxins.<br>o Pain with massage is a sign that rhabdomyolysis may be occurring. Do not continue massage therapy with pain.
 
= Differential Diagnosis  =
 
'''Rhabdomyolysis''': a clinical and biochemical syndrome resulting from skeletal muscle injury that alters the integrity of the muscle cell membrane sufficiently to allow the release of the muscle cell content into the plasma. Due to the quick breakdown of the skeletal muscle there is a big accumulation of the breakdown products which can cause renal failure. Although rhabdomyolysis is a symptom of McArdle’s disease, it can be a symptom of other conditions, or it can exist independently.
 
'''Fibromyalgia''': a syndrome characterized by widespread chronic unabated pain in addition to a host of several additional co-morbidities that can severely impact and disrupt a person’s daily life. The symptoms associated with fibromyalgia may originate from abnormal central nervous system output. Fibromyalgia isn't just one condition; it's a complex syndrome involving many different factors. McArdle’s Disease and Fibromyalgia share many symptoms, but they have different causes, so their treatments differ.
 
'''Muscular Dystrophy''': a group of more than 30 inherited diseases. They all cause muscle weakness and muscle loss. Some forms of MD appear in infancy or childhood. Others may not appear until middle age or later. The different types can vary in whom they affect, which muscles they affect, and what the symptoms are. All forms of MD grow worse as the person's muscles get weaker. Most people with MD eventually lose the ability to walk. McArdle’s Disease and Muscular Dystrophy share many symptoms, such as weakness and muscles loss.
 
'''Myositis''': Myositis means inflammation of the muscles that you use to move your body. An injury, infection, or autoimmune disease can cause it. Two specific kinds are polymyositis and dermatomyositis. Polymyositis causes muscle weakness, usually in the muscles closest to the trunk of your body. Dermatomyositis causes muscle weakness, plus a skin rash. Because Myositis also causes muscle weakness, it can present similarly to McArdle’s Disease.
 
'''Tarui's Disease''': A condition in which there exists a deficiency of the phosphofructokinase enzyme which is needed to facilitate the breakdown of glucose into energy in muscle during exercise. Tarui’s Disease is also a glycogen storage deficiency, so it has many similarities to McArdle’s Disease. Consequently, they are treated in a similar manner. <br>
 
= Case Reports/ Case Studies<br> =
 
Subjective: A 54-year-old man presented to physical therapy with a lifelong history of fatigability that worsened on exertion. Even as a child, he had experienced difficulty going up hills and lagged behind when he went out for a walk with friends. Since his childhood, he had been labeled as “lazy” by family and friends. He consulted several doctors, who were unable to provide an explanation for his symptoms, adding to his unhappiness and resulting in depression. He presented with early fatigue complaints and contractures triggered by dynamic exercise (climbing stairs) during a visit to his mother in hospital. He described a sensation of his legs becoming “stiff like a board” after walking for a while; this symptom was relieved by rest. These symptoms were worse if he was hungry and were alleviated after meals. There were no diurnal fluctuations in symptoms. There was no neuromuscular disease in his family history. He had depression and a long history of alcohol abuse. He had been receiving long-term treatment with tianeptine, bromazepam, omeprazole, and silymarin.
 
<br>Demographic Information: 54 y/o Male. Currently employed as a CPA<br>Co-morbidities: Obese, long history of alcohol abuse, 1 pack per day smoker<br>Previous care or treatment: Received physical therapy three years ago following R TKR <br>Self-Report Outcome Measures: Pain at rest 2/10. RPE with work 12. <br>Physical Performance Measures: During 5 Time Sit to Stand, pt expressed fatigue following one repetition.
 
<br>Objective: Findings of physical examination were unremarkable. At presentation, results of routine blood and chemistry tests showed a creatine kinase (CK) level of 7924 U/L, a lactate dehydrogenase level of 624 U/L, and a myoglobulin level of 671 ng/mL. A repeat check performed after cessation of treatment revealed a CK level of 2945 U/L. There was no myoglobinuria. Results of tests for autoimmune disease-related antibodies such as antinuclear antibody and anti-SSA, anti-SSB, and Topo-I antibodies were negative. Needle electromyography findings were normal at rest but upon volunteer effort, showed a myopathic pattern characterized by reduced duration and amplitude, and increased recruitment of potential short polyphasic motor units in the biceps and deltoid muscles. A test of sensory nerve conduction showed normal findings. A muscle biopsy specimen stained for glycogen showed subsarcolemmal accumulation of “lakes” of glycogen. Results of enzyme histochemistry were completely negative for myophosphorylase, confirming the diagnosis of McArdle disease (GSD V).<br>Case adapted from “McArdle Disease: A case report and review”<br>
 
= Recent Related Research (from [http://www.ncbi.nlm.nih.gov/pubmed/ Pubmed])  =
 
see tutorial on [[Adding PubMed Feed|Adding PubMed Feed]]  
<div class="researchbox"><rss>http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1LYeLHGBis05-KtP4MzBZOVvE_laSNnIZCGYGsFHuix8KCcooO|charset=UTF-8|short|max=10</rss></div>
<br>
 
= Resources <br>  =
 
*[http://www.agsd.org.uk/ Association for Glycogen Storage Disease UK]&nbsp;
*[http://www.agsdus.org/ Association for Glycogen Storage Disease US]
*[[Image:Facebook icon.gif|Image:Facebook_icon.gif]]&nbsp;[http://www.facebook.com/home.php#!/group.php?gid=2646925066 Join the Facebook Group: McArdle's Disease]
*[[Image:Nord.gif]]&nbsp;[http://www.inspire.com/groups/rare-disease/discussion/glycogen-storage-disease-v-mcardles-disease/ Support Community]
 
*[http://www.McArdlesDisease.org www.McArdlesDisease.org]&nbsp;
<div class="researchbox"></div>
= References  =
 
see [[Adding References|adding references tutorial]].
 
<br>
 
Special thank you to Andrew Wakelin, McArdle Disease (GSD Type V) Coordinator for AGSD UK&nbsp;for review and insight towards this page.
 
<br>
 
<references />
 
&nbsp;

Latest revision as of 15:28, 23 July 2023

Original Editors - Ed Foring as part of Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Edward Foring, Kaylynn Schwamb, Michael Helton, Lucinda hampton, Elaine Lonnemann, Kim Jackson, Admin, 127.0.0.1, Simone Potts and WikiSysop  

Definition/Description[edit | edit source]

Chromosome-DNA-gene copy.jpg

McArdle disease is a genetic disorder that mainly affects skeletal muscles. It occurs due to the deficiency or absence of an enzyme called myophosphorylase, a key substance that the muscles need to break down glycogen into sugar (glucose) for energy. Symptoms include painful muscle cramps, weakness, and fatigue manifested during periods of physical activity.[1] The disease can lead to dark urine.

  • Severe, uncontrolled McArdle disease can cause life-threatening kidney problems.[2]
  • To avoid the unpleasant symptoms associated with this condition and improve the quality of life, the disease requires prompt diagnosis and treatment.[1]

Etiology[edit | edit source]

McArdle disease typically results from mutations involving the muscle-specific isoform of the glycogen phosphorylase enzyme. This enzyme plays a key role in the first step of glycogenolysis that release glucose-1-phosphate monomers in muscle fibers. As a result, carbohydrate metabolism of the skeletal-muscle is affected, and energy cannot be generated from the glycogen stores of muscles.

Image 2:How muscle contraction differs in an unaffected muscle compared to one with McArdle’s Disease.

[3][4]

Epidemiology[edit | edit source]

The exact prevalence of McArdle disease is not precisely known and appears to range from 1 in 50,000 to 1 in 200,000 in the United States. [1]

Characteristics/Clinical Presentation[edit | edit source]

McArdle Disease patients can have critical episodes of early fatigue when exercising, muscle pain (myalgia), myoglobinuria (when muscles break down and release myoglobin in urine, making it brown/red in colour), and then subsequent kidney failure[5]. Some common symptoms of McArdle disease are:

  • Better able to do aerobic exercise after 8 to 10 minutes (second-wind phenomenon)
  • Brownish red urine, especially after periods of activity
  • Easily tiring during activity, with stiffness or weakness soon after starting exercise
  • Muscle cramping
  • Muscle pain
  • Lasting (permanent) weakness in the thigh or other muscles. This happens in a small portion of people with the condition.

Most of the time, people notice these symptoms before age 15. Often, people assume the symptoms are “growing pains” or due to some other cause. Different people may have symptoms of different severity eg person noticing that the symptoms seem worse or better at different times.[2]

Diagnosis[edit | edit source]

Some diagnostic tests include:

  • Blood tests to check for muscle enzymes, such as creatine kinase
  • DNA blood tests for known McArdle disease mutations
  • Electromyography to measure the electrical activity of the muscles
  • Forearm exercise test
  • MRI studies of your muscles
  • Muscle biopsy to examine the muscle cells for glycogen buildup
  • Urine tests to check for myoglobin, which darkens the urine[2]

Associated Co-morbidities[edit | edit source]

  • Renal Failure: Kidney dysfunction and failure are associated with rhadbomyolysis and myoglobinuria.
  • Gout: Inhibited ATP production leads to the production or purine metabolites. These metabolites are converted to uric acid, which can lead to hyperuricemia. [3][4][6]

Treatment[edit | edit source]

Fish.jpeg

Patients with McArdle Disease cannot utilise their glycogen energy stores in their skeletal muscles. Despite a great deal of intensive investigation, no effective treatment for McArdle Disease has been found.[5]

Image 3: Creatine rich food, most people get creatine through seafood and red meat (though at levels far below those found in synthetically made creatine supplements)

Persons may be able to use certain diet and exercise strategies to help control the problem. A well-designed low or moderate exercise routine may help the body get the most out of its' ability to use glucose. Overdoing exercise can harm the muscles and kidneys in people with McArdle disease. A healthcare team is vital in creating the best care plan for the situation. Some therapies used to help manage McArdle disease are:

  • Careful attention to a diet rich in carbohydrates
  • Creatine supplements
  • Eating or drinking prescribed amounts of sucrose before exercise
  • Prescribed, moderate aerobic exercise plan
  • Other medicines, such as ACE inhibitors

People with McArdle disease need to work with their care team and physio to establish a safe exercise plan.

There are currently no medications used to treat McArdle's Disease.[2]

Diet[edit | edit source]

Certain dietary interventions which confer favorable effects include taking a sugary meal before planning exercise - for example, having a drink containing 75g sucrose 40 minutes before exercise alleviates typical symptoms of exercise intolerance. A diet rich in carbohydrates results in much better outcomes in comparison to a protein-rich diet. Other nutritional agents that were helpful for some patients but could not yield convincing outcomes during actual experimental studies include branched-chain amino acids, depot glucagon preparations, verapamil, dantrolene sodium, vitamin B6, high dose D-ribose, and high-dose creatine ingestion.[1]

Physical Therapy Management[edit | edit source]

The physical therapist has an important role in keeping the patient active and avoiding inactivity due to fatigue.
Optimal exercise programs for managing McArdle’s Disease are aerobic based; they provide light resistance along with a cardiovascular component.

  • A plan of care incorporating low to moderate intensity aerobic physical activity can improve symptoms and reduce susceptibility to injury of the muscle.
  • The goal is to achieve the "second wind" for each muscle group that is being worked.
  • Light to moderate resistance training can also help, but allow adequate time to rest in between sets.
  • As a rule, do not work the muscles to absolute fatigue, and be sure to target larger muscle groups.
  • If strenuous activity must be done, use a 6 second rule. Only do that activity for 6 seconds prior to resting to ensure that only the phosphagen energy system is used in anaerobic activity.

Physical therapists can promote flexibility in order to prevent muscle contractures and reduce pain.

  • Stretching should be very light because maximal stretching will work the muscle anaerobically by inducing a protective contraction from the Golgi tendon. This strong protective contraction can lead to muscle damage.
  • Stretching following walking may offer immediate and dramatic pain relief to individuals with McArdle’s Disease.
  • For active individuals, stretching should take place very frequently to help reduce cramping. If not, muscles may become tight due to the toxic build up throughout activity and stretching can become painful.
  • Physical therapists should encourage a stretch that feels sufficient without causing pain.

Physical therapists should promote active participation by patients in managing their disease.

  • Individuals with McArdle’s Disease can easily overexert themselves and become injured without even realizing it.
  • It is important that they be conscious of their energy levels, blood sugar, heart rate, and general well-being.


For a brief discussion of treating a patient with McArdle's Disease, refer to the video below.


[7][8][7][9][10]

Alternative/Holistic Management[edit | edit source]

Massage: Individuals with McArdle’s Disease claim that massage therapy can be beneficial in maintaining an active lifestyle. Any massage should be light and fluid using effleurage techniques. Deep and hard massage for trigger point or myofascial release can be damaging to the muscle and should be avoided. Massages help push fatigue causing toxins out of the muscles and into the blood stream where they can be excreted from the body. It is recommended that individuals with McArdle’s Disease take in plenty of fluids following a massage to help flush the body of toxins. Pain with massage is a sign that rhabdomyolysis may be occurring. Do not continue massage therapy with pain.[3][4][11]

Differential Diagnosis[edit | edit source]

  • Rhabdomyolysis
  • Fibromyalgia
  • Muscular Dystrophy
  • Myositis
  • Tarui's Disease: A condition in which there exists a deficiency of the phosphofructokinase enzyme, which is needed to facilitate the breakdown of glucose into energy in muscle during exercise. Tarui’s Disease is also a glycogen storage deficiency, so it has many similarities to McArdle’s Disease. Consequently, they are treated in a similar manner. [8][3][4][12][13]

Case Study McArdle Disease[edit | edit source]

This case demonstrates some of the day-to-day struggles of living with McArdle's Disease along with associated signs and symptoms of the disease. It also discusses abnormal lab values and possible physical therapy interventions and outcomes

[14]

References[edit | edit source]

Special thank you to Andrew Wakelin, McArdle’s Disease (GSD Type V) Coordinator for AGSD UK for review and insight towards this page.

  1. ↑ 1.0 1.1 1.2 1.3 Khattak ZE, Ashraf M. McArdle Disease. StatPearls [Internet]. 2020 Aug 15. Available:https://www.statpearls.com/articlelibrary/viewarticle/24796/ (accessed 23.10.2021)
  2. ↑ 2.0 2.1 2.2 2.3 Cedars Sinai McArdle Disease Available: https://www.cedars-sinai.org/health-library/diseases-and-conditions/m/mcardle-disease.html (accessed 23.10.2021)
  3. ↑ 3.0 3.1 3.2 3.3 MedPoster 1992. nobelprize.org. [cited 3 April 2011]. Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/1992/illpres/glycogen.html
  4. ↑ 4.0 4.1 4.2 4.3 McArdlesDisease.org. [cited 17 March 2011]. Available from: www.mcardledisease.org
  5. ↑ 5.0 5.1 Brain Foundation McArdle Disease Award - 2012 Available: https://brainfoundation.org.au/research-grants/2012/mcardle-disease-award/ (accessed 23.10.2021)
  6. ↑ Driver MDCB. Gout Causes, Diet, Symptoms, Treatment & Medication [Internet]. MedicineNet. [cited 2017Apr5]. Available from: http://www.medicinenet.com/gout_gouty_arthritis/article.htm
  7. ↑ 7.0 7.1 Reference G. glycogen storage disease type V. Genetics Home Reference. 2017 [cited 18 March 2017]. Available from: https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v
  8. ↑ 8.0 8.1 Olafsen A. Quest - Article - McArdle’s Disease: The Right Diagnosis Can Lighten the Load - A Quest Article | Muscular Dystrophy Association. Muscular Dystrophy Association. 2017 [cited 18 March 2017]. Available from: https://www.mda.org/quest/article/mcardles-disease-diagnosis
  9. ↑ MedScape. [cited 19 April 2011]. Available from: http://www.medscape.org/viewarticle/581307_4
  10. ↑ Exercise for Homeschoolers [Internet]. Texas Rock Gym. [cited 2017Apr5]. Available from: http://www.texasrockgym.com/exercise-for-homeschoolers/
  11. ↑ Home [Internet]. Natural Tranquility Massage and Bodywork LLC. [cited 2017Apr5]. Available from: http://naturaltranquilitymassage.com/
  12. ↑ Baechle Thomas R and Roger W Earle. Essentials of Strength Training and Conditioning. Human Kinetics. Champaign,IL 2008.
  13. ↑ McArdle’s Disease (Glycogen Storage Disease Type V). Patient.info. 2017 [cited 18 March 2017]. Available from: http://patient.info/doctor/mcardles-disease-glycogen-storage-disease-type-v
  14. ↑ Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). 2017.
Retrieved from "https://www.physio-pedia.com/index.php?title=McArdle%27s_Disease&oldid=338880"