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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.]]  
<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 '''- Ed Foring&nbsp;[[Pathophysiology of Complex Patient Problems|from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  


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== Definition/Description<br> ==


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.  
== 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]].


<br>
* 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" />  


'''How Skeletal Muscles Normally Contract''' [[Image:Glycogen-metabolism.gif|left|1. Acetylcholine is released from a motor nerve. This causes an entry of calcium into the muscle cell.]]&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;'''&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;<span id="fck_dom_range_temp_1301880229521_645"></span><span id="fck_dom_range_temp_1301880229521_624"></span>A McArdle’s Disease Model'''
== 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.


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; [[Image:Energy 2.gif|Image:Energy_2.gif]]
Image 2:How muscle contraction differs in an unaffected muscle compared to one with McArdle’s Disease.<br>


<br>
[[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>  


<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: 707px; height: 150px" cellspacing="1" cellpadding="1" width="707" 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:
| 1. Acetylcholine is released from a motor nerve. This causes an entry of calcium into the muscle cell.
| 1. Acetylcholine is released from a motor nerve. This causes an entry of calcium into the muscle cell.
|-
| 2. Calcium activates phosphorylase kinase – the first protein kinase discovered by Fischer and Krebs.
| 2. Calcium activates phosphorylase kinase – the first protein kinase discovered by Fischer and Krebs.
|-
| 3. Phosphorylase kinase phosphorylates phosphorylase, which is activated
| 3. Phosphorylase kinase phosphorylates phosphorylase, which is missing or otherwise non-functional
|-
| 4. Glycogen is broken to glucose. This is used to generate ATP
| 4. Glycogen is unable to be broken down, creating glucose (and ATP) shortage.
|-
| 5. The muscle works and requires energy in the form of ATP
| 5. Motor proteins attach to muscle fibers require ATP for movement.
|-
| 6. The muscle contains muscle cells
| 6. Muscles stop responding in absence of ATP .
|-
| 7. Contractile proteins in the muscle are activated by calcium
| 7. Because ATP is required to both contract and relax muscles, injury can occur.
|}


<ref>MedPoster 1992</ref><ref>mcardlesdisease.org</ref>
* 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.


== Prevalence  ==
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" />


McArdle's disease is rare affecting approximately 1 in 100,000 people. This disease remains undiagnosed until most reach adulthood therefore the prevalence of this disease may be higher.
== Diagnosis ==
Some diagnostic tests include:


== Characteristics/Clinical Presentation  ==
* [[Blood Tests|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 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" />


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.  
== Associated Co-morbidities ==
*[[Chronic Kidney Disease|'''Renal''' '''Failure''']]: Kidney dysfunction and failure are associated with rhadbomyolysis and myoglobinuria.


'''Premature Exhaustion: S'''keletal 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.  
*'''[[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 ==
[[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" />


'''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.
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)


'''Cramping:''' Muscle failure leads to electrically-silent contractures which are very painful and can lead to muscle damage.
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:


'''[http://www.wikidoc.org/index.php/Myoglobinuria Myoglobinuria]: '''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. Myoglobinuria has lead to renal dysfunction, therefore cramping and muscle failure episodes require medical attention.
* Careful attention to a diet rich in carbohydrates
* [[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


'''Fixed Weakness:''' Muscle damage caused by [http://www.physio-pedia.com/index.php5?title=Rhabdomyolysis rhabdomyolysis] can lead to muscle weakness that seems to not get physically stronger or is extremely difficult to make strength gains.  
People with McArdle disease need to work with their care team and physio to establish a safe exercise plan.  


'''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.
There are currently no medications used to treat McArdle's Disease.<ref name=":1" />


== Associated Co-morbidities  ==
== 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" />


add text here <br>
== Physical Therapy Management ==
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.


== Medications  ==
*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>


add text here <br>
'''Physical therapists can promote flexibility in order to prevent muscle contractures and reduce pain.'''


== Diagnostic Tests/Lab Tests/Lab Values  ==
*[[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.


'''Ischemic Forearm Test <br>'''This test is a valuable diagnostic test for a number of metabolic diseases. This 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:&nbsp;
'''Physical therapists should promote active participation by patients in managing their disease.'''  


''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.''
*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.


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


'''Muscle Biopsy''' <br>The following is a description of a muscle biopsy performed in order to diagnose McArdle’s disease in an elderly patient. It involves microscopic muscle fiber examination to identify, among other characteristics, large deposits of glycogen:


<br>Biopsy of Left quadriceps was performed. The biopsy showed subsarcolemmal vacuoles in many fibers with no abnormal contents on hematoxylin and eosin (fig. 1A), Masson’s trichrome (fig. 1B) or Gomori stains (Fig.1C). Increased glycogen content (Fig. 2A) was present in several fibers on PAS stain (diastase sensitive). Myophosphorylase activity was absent using enzyme histochemistry (fig. 2B) with a positive control (Fig. 2C). Mild to moderate myopathic features were present including increased fiber size variation and internal nucleation (Fig. 3A) with scattered myofiber hypertrophy and occasional fiber splitting (fig. 3B). Type I fiber smallness was suggested on ATPse stains (fig. 3C). Decreased oxidative enzymes staining with “moth-eaten” appearance was present, mostly in type 1 fibers (fig. 4A) with linearization of the intermyofibrillar architecture in type II fibers (Fig. 4B). Neurogenic atrophy was minimal.  
<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>


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.]
== 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 ==


'''CP/CPK Lab Values'''
* [[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>


If lab work is conducted than the patient will have an elevated [http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm 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&nbsp;inability of glycogen&nbsp;to turn into&nbsp;glucose for energy; the muscle breaks down itself releasing this enzyme into the blood stream.
==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


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


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. Several genetic mutations have been found to be the reason why this enzyme is missing or non-functioning. <br>
== References ==


== Systemic Involvement  ==
Special thank you to Andrew Wakelin, McArdle’s Disease (GSD Type V) Coordinator for AGSD UK for review and insight towards this page.  
 
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://www2.cochrane.org/reviews/en/ab003458.html 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>
 
 
 
[http://mcardlesdisease.org/information-about-mcardles-disease/the-only-realistic-treatment-for-mcardles-disease/ The Only Realistic Treatment for McArdles Disease]
 
- This link brings you to an excerpt off the mcardlesdiease.org website.
 
<ref>mcardlesdiease.org</ref>
 
== Physical Therapy Management (current best evidence)  ==
 
'''Be Fit<br>'''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. <br>'''Be Flexible<br>'''Stretching following walking offers immediate and dramatic pain relief to individuals. Stretching also promotes flexibility in areas that may have become inflexible.<br>'''Be Aware, Be Patient and WARM UP<br>'''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  ==
 
add text here
 
== 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 : 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>
 
 
 
 
 
add links to case studies here (case studies should be added on new pages using the [[Template:Case Study|case study template]])<br>
 
== Resources <br> ==
 
Please visit [http://www.McArdlesDisease.org www.McArdlesDisease.org] to read blog post written by people living with this disease. These blog post written by people that suffer from the disease include signs and symptoms prior to diagnosis, how they were diagnosed, how they manage their disease, and how to manage an active lifestyle with this disease. This on going blog on [http://www.McArdlesDiease.org www.McArdlesDiease.org] also allows you the opportunity to post and insight you may have on this disease or communicate with others about this disease.
 
== 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>Feed goes here!!|charset=UTF-8|short|max=10</rss>
</div>
== References  ==
 
see [[Adding References|adding references tutorial]].  


<references />
<references />
 
[[Category:Conditions]]
McArdlesDisease.org.&nbsp;[http://www.mcardledisease.org www.mcardledisease.org] (accessed&nbsp;17 March 2011).&nbsp;
[[Category:Paediatrics - Conditions]]
 
[[Category:Genetic Disorders]]
Myoglobinuria. Wikidoc.&nbsp;[http://www.wikidoc.org/index.php/Myoglobinuria http://www.wikidoc.org/index.php/Myoglobinuria] (accessed 17 March 2011).
 
MedPoster 1992. nobelprize.org.&nbsp;[http://nobelprize.org/nobel_prizes/medicine/laureates/1992/illpres/glycogen.html http://nobelprize.org/nobel_prizes/medicine/laureates/1992/illpres/glycogen.html]&nbsp;(accessed 3 April 2011).
 
Geneva Foundation for Medical Education and Research. Glycogen Storage disease V.&nbsp;[http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=912 http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=912]&nbsp;(accessed 3 April 2011).
 
Medline Plus. Creatine Phosphokinase test.[http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm]&nbsp;(accessed 3 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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