In childhood, the onset of symptoms may be noticed, but most often the diagnosis is made in the third or the fourth decade of life. Most people suffering from this disease appear physically fit and healthy though they may undergo premature fatigue, weakness, and pain during exercise. Hence, it is assumed that the person is out of shape or unwilling to exercise. When an individual suffering from GSD5 exercises, they experience fatigue, muscle pain, cramps, etc. within the first few minutes of exercise. Weight lifting or jogging usually trigger these symptoms in such an individual. Taking rest ameliorates the symptoms. This can be followed by a ‘second-wind phenomenon’ . After exercising the affected person feel fatigued, but if he slows down or stops and allows the pain to reduce then he can resume exercises again without previous discomfort or pain. According to Braakhekke and colleagues, this may be resultant due to increased recruitment of motor units, improved cardiac output, and the use of free fatty acids for muscle metabolism . When patients with GSD5 continue exercises for a long duration without rest or perform intense exercises, rhabdomyolysis and consequent myoglobinuria may occur causing renal dysfunction and eventually leading to acute renal failure. Voduc and colleagues have reported unexplained dyspnoea as a symptom of GSD5 . In rare cases, early-onset with generalized muscle weakness, hypotonia, and progressive respiratory failure has been reported.
Entire Body System
- Difficulty Climbing Stairs
No sport activities were possible and the boy had even difficulties climbing stairs due to muscle weakness. Moreover, he complained of chest pain after physical exercise and recurrent nausea. [ojrd.biomedcentral.com]
- Intravenous Administration
The effects of intravenous and oral glucose are not necessarily similar, because the absorption of glucose and the neurohormonal responses to it depend on the route of administration. 19 In this study we investigated whether patients with McArdle's disease [doi.org]
Kelly Webb, 36, of Demopolis, Ala., collapsed without warning while swimming and almost drowned when she was 5 or 6. [mda.org]
Haller, Metabolic and Mitochondrial Myopathies, Neurologic Clinics, 32, 3, (777), (2014). [doi.org]
McArdle: Myopathy due to a defect in muscle glycogen breakdown. Clinical Science, London, 1951, 10: 13-33. R. Schmid, R. Mahler: Chronic progressive myopathy with myoglobinuria: demonstration of a glycogenolytic defect in the muscle. [whonamedit.com]
Creatine kinase levels were elevated, serum lactate did not rise on ischemic exercise testing, and muscle biopsy showed a vacuolar myopathy with absent myophosphorylase activity. [ncbi.nlm.nih.gov]
- Muscle Weakness
- Muscle Cramp
Under these circumstances, the body breaks down muscle when trying to attain energy. This causes many symptoms such as muscle pain, muscle cramping, muscle fatigue, and muscle tenderness. [web.archive.org]
Up to 85% of patients can be confirmed without muscle biopsy. [ 4 ] Electromyography: may show nonspecific myopathic changes or increased muscle irritability. Electrical activity may be absent during exercise-induced muscle cramps. [patient.info]
Muscle cramps following exercise Muscle cramps on exercise Muscle cramps on exertion Muscle cramps with exertion [ more ] 0003710 Exercise-induced myalgia Exercise-induced muscle pain Muscle pain on exercise Muscle pain with exercise Muscle pain, exercise-induced [rarediseases.info.nih.gov]
Ischemic forearm exercise invariably causes muscle cramps and pain in patients with glycolytic defects. We investigated an alternative diagnostic exercise test that may be better tolerated. [ncbi.nlm.nih.gov]
Patients experience early onset of fatigue and muscle pain with exercise. The body breaks down muscle when trying to attain energy, which causes many symptoms such as muscle pain, muscle cramping, muscle fatigue, and muscle tenderness. [mda.org.au]
He had no history of exercise-induced cramps, myalgias, or myoglobinuria. [ncbi.nlm.nih.gov]
He had no history of exercise‐induced cramps, myalgias, or myoglobinuria. [doi.org]
Patients present with a syndrome of muscular exercise intolerance with myalgia, cramps, fatigue, and muscle weakness. [orpha.net]
- Muscle Contracture
Most patients experience muscle symptoms, such as weakness and cramps, although certain GSDs manifest as specific syndromes, such as hypoglycemic seizures or cardiomegaly. The diagram below illustrates metabolic pathways of carbohydrates. [emedicine.medscape.com]
This disease principally affects the liver. It causes swelling of the liver, slowing of growth, low blood sugar levels and, sometimes, seizures. [slideshare.net]
Common symptoms include: Protruding abdomen from an enlarged liver and seizures from low blood sugar are common in infants Signs of low blood sugar including Paleness Irritability Fatigue Seizures Growth delay Copyright © Nucleus Medical Media, Inc. [cancercarewny.com]
Creatine kinase levels are high in about 90% of cases suffering from GSD5. It may be the only sign of the disease. Urine testing is advised since myoglobinuria is present in about 50% of GSD5 patients. The ischemic forearm test reveals a lack of lactate elevation in blood. The muscle biopsy confirms the absence of myophosphorylase activity. Molecular genetic testing may be done to determine the presence of gene mutations on the PYGM gene.
Phenotype and clinics Patients have poor tolerance to fasting (with hypoglycemia and hyperlactacidemia after 3 to 4 hours of fasting), marked hepatomegaly, full-cheeked round face, growth retardation (small stature and delayed puberty), generally improved [atlasgeneticsoncology.org]
- Creatine Phosphokinase Increased
[…] serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ] 0003236 30%-79% of people have these symptoms Myopathy Muscle [rarediseases.info.nih.gov]
A patient suffering from GSD5 must not perform any strenuous workouts like lifting weights, pushing heavy objects or intense gym exercises, etc. However, it is important to perform controlled physical training like walking regularly to keep fit and healthy. A healthy diet and weight control are also recommendable.
GSD5 by itself is not a life-threatening disease. Patients with the condition are generally in good health. If rhabdomyolysis is avoided, then the prognosis is good. If myoglobinuria is experienced then it can lead to acute renal failure and death. Death can also occur due to respiratory failure in cases of severe muscle weakness. Genetic counseling is a must for patients as it is a genetic disorder.
Glycogen storage disease Type 5 involves mutations of the PYGM gene located on 11q13 chromosome leading to muscle phosphorylase deficiency. GSD 5 has two autosomal recessive forms, a childhood-onset form, and an adult-onset form.
GSD5 is a rare autosomal recessive disease. The heterozygote forms are usually asymptomatic. The prevalence is estimated at around 1 per 100,000 population. The mildness of the symptoms in patients has caused it to be an under-diagnosed disorder. The majority of cases are diagnosed in the second to third decade of life.
Wolfe and colleagues have documented a unique case presenting in a person at an age of 73 years . Felice and colleagues and Pourmand and colleagues also have documented late presentations of GSD5 cases. This suggests that doctors should have clinical suspicion irrespective of the age of presentation  .
The PYGM gene is involved in the production of an enzyme called myophosphorylase which breaks down glycogen into glucose-1-phosphate, a simple form of sugar, then converted to glucose.
Being an inherited genetic defect, there is no way to prevent or reverse the condition.
Glycogen storage disease Type 5 (McArdle disease or GSD5) is one among the many in a group of inherited glycogen storage diseases. Specific enzymes catalyze reactions that help convert glycogen to glucose. Many different mutations have been reported for each type of GSD . The deficiency of these enzymes causes glycogen accumulation in tissues leading to systemic outcomes or specific tissue-related outcomes . GSD 5 is an inherited autosomal recessive disease and the deficient enzyme is myophosphorylase . The disease was first reported in 1951 by Dr. Brian McArdle of Guy's Hospital, London. GSD 5 has two autosomal recessive forms, a childhood-onset form, and an adult-onset form.
Glycogen storage disease type 5 (GSD5) is a genetic disorder. It is caused due to the deficiency of enzyme myophosphorylase. Most people with GSD5 may suffer from it since childhood but it goes undiagnosed till adulthood. People with GSD5 usually appear physically healthy but suffer from fatigue post exercises. This can be confused with being not fit or disinclined to exercise. Hence, symptoms of GSD5 are usually detected in the second or third decade of life. Fatigue, pain, and weakness with strenuous activities like jogging, swimming, or even walking are the characteristic symptoms of the disease. However, if they stop their activity and rest, then they can resume the physical exertion probably because the body uses other sources of energy production. This is known as the second-wind phenomenon. In cases when strenuous exercise is continued it leads to rapid muscle breakdown called rhabdomyolysis. This causes the release of proteins like creatine kinase and myoglobin in the urine causing it to turn dark red or brown called myoglobinuria. This can lead to acute kidney failure.
Diagnosis can be made from the history of the patient. Physical examination may not reveal many abnormal findings. Tests advised include creatine kinase testing, urine analysis, ischemic forearm test, and muscle biopsy. The biochemical assay is a confirmatory test for the enzyme activity.
Affected persons must remember to mention the disease whenever you visit any medical setup. A balanced diet rich in protein and vitamins aids to improve muscle tolerance. GSD5 patients must avoid strenuous exercises. Though they must continue light exercises and stretches to improve muscle strength and flexibility.
- Duno M, Quinlivan R, Vissing J, et al. High-resolution melting facilitates mutation screening of PYGM in patients with McArdle disease. Ann Hum Genet. May 2009;73:292-7.
- Rubio JC, Garcia-Consuegra I, Nogales-Gadea G, et al. "A proposed molecular diagnostic flowchart for myophosphorylase deficiency (McArdle disease) in blood samples from Spanish patients". Hum. Mutat. 28 (2): 203–4.
- Dimaur S, Andreu AL, Bruno C, et al. Myophosphorylase deficiency (glycogenosis type V; McArdle disease). Curr Mol Med. 2002 Mar;2(2):189-96.
- Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan;105(1):e10.
- Wolfe GI, Baker NS, Haller RG. McArdle's disease presenting with asymmetric, late-onset arm weakness. Muscle Nerve. Apr 2000;23(4):641-5.
- Felice KJ, Schneebaum AB, Jones HR Jr. McArdle's disease with late-onset symptoms: case report and review of the literature. J Neurol Neurosurg Psychiatry. May 1992;55(5):407-8.
- Pourmand R, Sanders DB, Corwin HM. Late-onset Mcardle's disease with unusual electromyographic findings. Arch Neurol. Jun 1983;40(6):374-7.
- Orngreen MC, Jeppesen TD, Andersen ST, et al. Fat metabolism during exercise in patients with McArdle disease. Neurology. Feb 24 2009;72(8):718-24.
- Braakhekke JP, de Bruin MI, Stegeman DF. The second wind phenomenon in McArdle's disease. Brain. 109 (Pt 6):1087-101.
- Voduc N, Webb KA, D'Arsigny C, et al. McArdle's disease presenting as unexplained dyspnea in a young woman. Can Respir J. Mar 2004;11(2):163-7.