McArdle's Disease: Difference between revisions

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<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.]]  
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'''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.]]  


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== 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]]. 


In 1951 Dr. Brain McArdle of Guy's Hospital in London England first described this disease. This disease also is refered to as&nbsp;myophosphorylase deficiency or Type V glycogen storage disease. This disease is a metabolic disease where skeletal muscle cells&nbsp;can not breakdown glycogen into glucose.  
* 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" />


<br>
== 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.


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


== '''<u>Definitions</u>'''  ==
*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, [[Pulse rate|heart rate]], and general well-being.


'''Bioenergetics:''' flow of energy in a biological system, concerned primarily with the conversion of macronutrients - carbohydrates, proteins, and fats, into usable forms of energy.


'''Catabolism:''' breakdown of large molecules into smaller molecules, associated with the release of eneergy.  
For a brief discussion of treating a patient with McArdle's Disease, refer to the video below. {{#ev:youtube|qsnDu-fLdRs}}


'''Anabolism: '''synthesis of larger molecules from smaller molecules, accomplished with the energy released from catabolic reactions.


'''Exergonic Reactions:''' energy releasing reactions, generally catabolic
<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>


'''Endergonic Reactions:''' require energy and included in the anabolic process and contraction of muscle
== 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 ==


'''Metabolism: '''Is the total exergonic and endergonic reactions in a system.  
* [[Rhabdomyolysis]]
* [[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>


'''ATP&nbsp;: '''Adenosine Triphosphate allows the transfer of energy from exergonic to endergonic reactions. Without adequate supply muscle activity or growth is not possible.
==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


'''ATP+H<sub>2</sub>O &lt;-------&gt; ADP + P + H<sup>+</sup>+ Energy'''
<ref name="p9">Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). 2017.</ref>


'''(ADP - adenosine diphosphate, P- Phosphate , H<sup>+ </sup>- Hydrogen)'''
== References ==


<br>'''Hydrolysis: '''Breakdown of ATP with a water molecule to form energy.
Special thank you to Andrew Wakelin, McArdle’s Disease (GSD Type V) Coordinator for AGSD UK for review and insight towards this page.  
 
'''Anaerobic: '''Process does not require the presence of oxygen
 
'''Aerobic:''' Process is dependent on oxygen.<span id="fck_dom_range_temp_1303275706480_835"></span>
 
'''Mitochondria:''' power house of the cell in which the Kreb cycle take place.
 
'''<u></u>'''
 
== '''<u>Three Basic Energy System</u>'''  ==
 
=== '''Phosphagen System'''  ===
 
*Anaerobic mechanism that occurs in the sarcoplasm of a muscle cell
*Provides ATP primarily for short term, high intensity activities
*Active at the start of all exercise regardless of intensity
*Relies on hydrolysis of ATP and breakdown of creatine phosphate (CP)
*CP supplies a phosphate group to ADP to replenish ATP
*CP stored in small amounts so can not sustain continuous, long duration activitie
 
=== Glycolysis [[Image:Glycolysis1.jpg|thumb|right]]  ===
 
*Breakdown of carbohydrates - either glycogen stored in the muscle or glucose delievered in the blood- to resynthesize ATP.
*ATP production during glycolysis is not as rapid with the phosphagen system, however capacity is much higher due to the stores of glycogen and glucose.
*End product of glycolysis are pyruvate. Pyruvate can either be converted to lactate or be shuttles into the mitochondria.
*'''Anerobic glycolysis or Fast glycolysis:''' pyruvate is converted into lactate, ATP production is rapid but short in duration. This energy system is typically trained in sprinters or resistance training.
*'''Aerobic glcolysis or Slow glycolysis: '''pyruvate is shuttled into the mitochrondria, converted to Acetyl CoA and than enters the Kreb Cycle. ATP resynthesis is slow but can occur for a long duration if the exercise intensity is low. This energy system is typically trained in long distance runners or aerobic activity.
 
*'''Phosphorylation:''' if the process of adding an inorganic phosphate to another molecule. There are two primary phosphorylations mechanism used to resynthesize ATP.
*'''Oxidative Phosphorylation:'''&nbsp; is the resynthesis of ATP in the electorn transport chain. NADH and FADH<sub>2</sub> are by-products of fatty acids and amino acids converting to pyruvate, acetyl CoA, oxaloaceate, succinyl- CoA, and ketoglutarate so they can enter the Kreb Cycle. NADH and FADH<sub>2</sub> are used to rephosphorylate ADP to ATP. This is where the "second wind" that McArdle's patients experience is derived from.
 
=== The Oxidative System&nbsp;  ===
 
*This is the aerobic system and the primary source of ATP at rest and low-intensity activities.&nbsp;
*This system uses primarily carbohydrates and fats as substrates, but proteins will be metabolized during long-term starvation and long bouts of exercise. Since carbohydrate metabolism can not occur in McArdle's patients they primarily function with blood glucose metabolism, fat metabolism, and than ultimately protein metabolism which can lead to rhabdomyolysis.
*At rest 70% of ATP production comes from fats and 30% from carbohydrates
*High Intensity aerobic activity is almost 100% carbohydrates.
*Pro-longed submaximal, steady state work, there is a gradual shift from carbohydrates back to fats and proteins for energy.
*Oxidative metabolism of blood Glucose and muscle glycogen begins with glycolysis. The end product pyruvate is than converted to Acetyl-CoA and than enters the Kreb cycle. Oxidation of the substrate, substrate-level phosphorylation, yields ATP. By prodcuts NADH and FADH<sub><span id="1303280601145S" style="display: none">&nbsp;2</span></sub><span style="display: none"> enter the electron transport train. Total yield is 38 ATP. </span>
*<span style="display: none">Triglycerides stored in fats can be broken down by hormone sensitive lipase. This releases fatty acids from the fat cells into the blood, where they can than circulate and enter the muscles. Fatty acids enter the mitochondria where they undergo beta oxidation, breaking down the fatty acids into acetyl-CoA and hydrogen protons. Acetyl-CoA enter the Kreb cycle and hydrogen atoms attach to NADH and FADH<sub>2</sub> and enter the electron transport chain. Total yield is 463 ATP</span>
*<span style="display: none">Proteins can be brokendown into amino acids by various metabolic processes. These amino acids can be converted to glucose, pyruvate, and various Kreb cycle intermediates. The major amino acids believes to be oxidized in skeletal muscle are BCAA (branches chained amino acids) which are leucine, isoleucine, and valine. The waste products amino acid degradation is urea and small amounts of ammonia. This can lead to hyperuricemia in McArdle's patients resulting in gout. Urea and ammonia are also toxic to skeletal muscle and results in fatigue. </span>
 
= Prevalence  =
 
McArdle's disease is rare affecting approximately 1 in 100,000 people. It presents in the second to third decade of life with symptoms reported at childhood.
 
<ref name="MDORG" />
 
= Characteristics/Clinical Presentation  =
 
Symptoms typically present 10 seconds after strenous exercise has begun. After 10 seconds of exercise skeletal muscle relies on the conversion of glycogen to glucose to produce ATP which is the main energy source to power muscular contraction.
 
'''Premature Exhaustion: '''Skeletal muscles inability to metabolize glycogen into glucose with strenous activity leads to an abrupt feeling of exhaustion or fatigue, with an increase in heart rate. Individuals might complain of diffculty walking, jogging, ascending and descending steps, or any moderate levels of activity.
 
'''Muscle Failure:''' This particularly occurs under extreme stress where the muscle no longer can produce contraction regardless of the effort made. This is compaired to "wall" runners experience when doing a marathon.
 
'''Cramping:''' Muscle failure leads to electrically-silent contractures which are very painful and can lead to muscle damage.
 
'''[http://www.physio-pedia.com/index.php5?title=Rhabdomyolysis Rhabdomyolysis]: '''Damage to muscle tissue leads to the release of proteins,creatine kinase and myoglobin, into the blood&nbsp;which are than excreted with urination. These proteins are iron-rich and may cause urine to be a redish color. This symptom is refered to as myoglobinuria. [http://www.wikidoc.org/index.php/Myoglobinuria Myoglobinuria] has lead to renal dysfunction, therefore cramping and muscle failure episodes require medical attention.
 
'''Fixed Weakness:''' Muscle damage caused by rhabdomyolysis can lead to muscle weakness that seems to not get physically stronger or is extremely difficult to make strength gains.
 
'''Muscle Wasting:''' Muscle atrophy
 
'''Second Wind:''' The phenomenon has been observed in clincal trials in patients after following a "warm up" period. This second wind does not relieve failure symptoms for intense exercise but offers some relief for light to moderate exercise.
 
<ref>Myoglobinuria. Wikidoc. http://www.wikidoc.org/index.php/Myoglobinuria (accessed 17 March 2011).</ref><ref name="MDORG" /><br>
 
&nbsp;<span id="fck_dom_range_temp_1303265919131_672"></span><span id="fck_dom_range_temp_1303265919131_748"></span>
 
= Associated Co-morbidities  =
 
*[http://www.wikidoc.org/index.php/Myoglobinuria Myoglobinuria] a symptom of McArdle's disease can lead to renal failure and therefore should be screened for.
*[http://www.niams.nih.gov/Health_Info/Gout/default.asp Gout]: Inhibited ATP production leads to the production or purine metabolites. Purine metabolites are than converted to uric acid leading to hyperuricemia. 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.
 
<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>
 
= Medications  =
 
There are no medications right now that are used to treat McArdle's Disease.
 
*Oral B<sub>6</sub> vitamins are suggested to help reduce the impairment of fatigue.
*Patients are also recommended to eat a high protein diet to help reduce muscle breakdown.
*Sucrose treatment prior to exercise is also recommended
 
= 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  =
 
The cause of this diseas<span id="fck_dom_range_temp_1300418515912_890"></span><span id="fck_dom_range_temp_1300418515913_925"></span>e is due to a missing or non-functioning enzyme that breaks down glycogen into glucose during exercise called&nbsp;myophosphorylase C. Genetic involvement shows an autosomal recessive inheritance pattern, requiring two defective copies of the gene for the condition to manifest. Carriers are not known to have symptoms of the disease.<br><br>
 
= 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.
 
= 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)  =
 
One of the biggest roles a physical therapist can provide is keeping the person active because inactivity due to fatigue is very common in patients with McArdle's Disease.
 
<u>'''Be Fit'''</u>
 
*A&nbsp;disciplined regimen of regular physical activity of the appropriate intensity and duration can improve symptoms and&nbsp;reduce susceptible of injury to the muscle.
*Light to moderate resistance training can be done but give adequate time to rest inbetween sets,don't work the muscles to absolute fatigue, and work big muscle groups.
*Certain physicians will recommend having a high sugary food before or while exercising but this is considered debatable. [http://quest.mda.org/article/clinical-trials-and-studies-march-april-2004 Click&nbsp;here to read more&nbsp;on this.&nbsp;]
*Optimal exercises programs for managing McArdles Disease are aerobic based due that they provide light resistance but still include a cardiovascular component.
 
<u>'''Be Flexible'''</u>
 
*Stretching following walking offers immediate and dramatic pain relief to individuals.
*Stretching also promotes flexibility in areas that may have become inflexible.
*For active individuals stretching might have to take place very frequently to help reduce cramping.
*Due to the toxic build up in the muscle from activity, muscles will become tight and therefore stretching can become painful.
*It is recommended that stretches are held for atleast 30 seconds for several repetitions and repeated through out the day as necessary.
 
<u>'''Be Aware, Be Patient and WARM UP'''</u>
 
*Individuals can easily over exhert themselves and become injuried without even realizing it.
*Indivduals need to be conscious of their energy levels, their blood sugar, their heart rate, and their general well being.
*Individuals should not avoid physical activity altogether, but&nbsp;if they are faced with a strenous task they should be instructed to take their time with it.&nbsp;
*During any type of strenous activity they should be instructed to warm up properly and periodically do several boughts of stretches.
 
= Alternative/Holistic Management (current best evidence)  =
 
Individuals that live with this disease claim that a massage therapist with weekly sessions is necessary to remain active. Due to the nature of this disease alot of toxic byproducts are released when the muscles experience activity. Massage therapist help push the toxins out of the muscles and into the blood stream where they can be&nbsp;excreted from the body. Individuals with the disease claim the massage can be painful and uncomfortable but in necessary to live an active lifestyle.
 
= Differential Diagnosis  =
 
*[http://www.physio-pedia.com/index.php5?title=Rhabdomyolysis Rhabdomyolysis]
*[http://www.physio-pedia.com/index.php5?title=Fibromyalgia Fibromyalgia]
*[http://www.nlm.nih.gov/medlineplus/musculardystrophy.html Muscular Dystrophy]
 
= Case Reports/ Case Studies  =
 
[http://www.ispub.com/journal/the_internet_journal_of_neurology/volume_9_number_1_6/article/diagnosis_of_mcardle_s_disease_in_an_elderly_patient_case_report_and_review_of_literature.html R. Makary, A. Berger, N. Talpur &amp; S. Shuja&nbsp;: Diagnosis of McArdle's disease in an elderly patient: Case report and review of literature . The Internet Journal of Neurology. 2008 Volume 9 Number 1]<br>
 
<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> =
 
*[[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.agsdus.org/ Association for Glycogen Storage Disease US]
*[http://www.agsd.org.uk/ Association for Glycogen Storage Disease UK]
 
*[http://www.McArdlesDisease.org www.McArdlesDisease.org]&nbsp;
<div class="researchbox"></div>
= References  =
 
see [[Adding References|adding references tutorial]].  


<references />
<references />
 
[[Category:Conditions]]
&nbsp;
[[Category:Paediatrics - Conditions]]
 
[[Category:Genetic Disorders]]
Second Wind. [http://www.mda.org www.mda.org].&nbsp;[http://www.mda.org/publications/images/q11-4_Chart2.jpg] (accessed 5 April 2011)
 
Association for Glycogen Storage Disease.&nbsp;[http://www.agsdus.org http://www.agsdus.org] . (accessed 5 April 2011).
 
[http://nobelprize.org/nobel_prizes/medicine/laureates/1992/illpres/glycogen.html Category:Bellarmine_Student_Project]

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.
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