Glycogen storage disease type 5 (GSD5), also known as Myophosphorylase deficiency or McArdle's disease, is a rare inherited metabolic disorder, characterized by exercise intolerance.
The age at which the symptoms of Glycogen Storage Disease type 5 become visible is dependent on the enzyme activity level. In childhood, the onset of symptoms may be noticed, but most often the disease diagnosis happens only 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.
The severity of the disease depends on the enzyme activity; hence, each individual will present the signs and symptoms differently.
When an individual suffering from Glycogen Storage Disease type 5 exercises they undergo fatigue, muscle pain, cramps etc. within 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 individuals undergo fatigue, 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 use of free fatty acids for muscle metabolism .
When patients with Glycogen Storage Disease type 5 continue exercises for long duration without rest or perform intense exercises then their muscles get damaged causing rhabdomyolysis i.e. rapid muscle breakdown with muscle contractures. In severe cases, proteins like creatine kinase and myoglobin are released which filter through the kidneys and pass in urine causing urine to be red or brown in colour called myoglobinuria. This protein can cause renal dysfunction and eventually leading to acute renal failure.
Voduc and colleagues have reported one of the symptoms as unexplained dyspnoea .
On physical examination one may not find any positive clinical findings. Also, the muscle strength and reflexes tend to be normal. Glycogen Storage Disease type 5 in infants is fatal and presents with hypotonia and reduced reflexes.
Creatine kinase levels are high in about 90% cases suffering from Glycogen Storage Disease type 5. It may be the only sign of the disease. Hence, it is important to check the level of creatine kinase in all suspected cases of Glycogen Storage Disease type 5.
Urine testing is advised since myoglobinuria is one of the presentations in about 50% of patients of Glycogen Storage Disease type 5.
To diagnose muscle disorders, one the main tests is the ischemic forearm test. The aim is to study the normal chemical reactions and the outcome of muscle activity. Blood tests to check levels of creatine kinase, ammonia and lactate and urine analysis for myoglobin are performed. Then a blood pressure cuff is tied around the patient’s arm & inflated. The patient is asked clutch an object firmly. This is continued till he can no longer perform it. Then the cuff is removed and blood samples taken at next 5, 10 and 15 minutes. Also, one urine sample is collected.
When one exercises, lactate is produced through carbohydrate metabolic pathways. If there is no or minimal rise in lactate concentration along with ammonia then it suggests presence of myophosphorylase deficiency i.e. Glycogen Storage Disease type 5.
The biopsy checks the presence of myophosphorylase activity. This is absent in GSD V which confirms the diagnosis.
Biochemical assay is confirmatory test for detecting enzyme activity.
In northern Europe 85% patients show an abnormal gene encoding for muscle phosphorylase. DNA testing is supposed to be less invasive then muscle biopsy.
When one suffers from Glycogen Storage Disease type 5, there are certain cautions one must follow. Like when going in for any operation it is important to mention about your disease to the anaesthetists and the concerned physicians. This is necessary so that they will then avoid some anaesthetic agents and other drugs which can be harmful. Also, they will not use tourniquets during any procedure.
A patient suffering from Glycogen Storage Disease type 5 must not perform any strenuous workouts like lifting weights, pushing heavy objects or intense gym exercises etc. However, it is important to perform simple exercises like walking regularly to keep fit and healthy.
When the patient starts exercising if he experiences any pain, it is important to stop otherwise it will increase the risk of myoglobinuria which can end in acute renal failure .
In case of myoglobinuria one must drink plenty of fluids to flush out the proteins.
A diet which is rich in proteins diet may help to boost tolerance to exercises. Some studies suggest Vitamin B6 helps to improve resistance to fatigue .
Glycogen Storage Disease type 5 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. Though not common but some cases do suffer from seizures.
When Adenosine monophosphate (AMP) along with hypoxanthine and xanthine is produced in excess and released in the blood lead to hyperuricaemia.
Genetic counselling is a must for patients who suffer from Glycogen Storage Disease type 5 as it is a genetic disorder.
Glycogen Storage Disease type 5 is a rare autosomal recessive disease. The heterozygote forms are usually asymptomatic. Chromosome 11 contains the gene for myophosphorylase .
The prevalence of Glycogen Storage Disease type 5 is around 1 per 100,000 population. The mildness of the symptoms in patients has caused it to be an under diagnosed disorder. Hence, only a few hundred cases have been accounted.
The overall prevalence of all GSDs is about 2.3 children per 100,000 births per year . Majority cases of Glycogen Storage Disease type 5 usually present the symptoms in the second to third decade of life.
Wolfe and colleagues have documented a unique case of Glycogen Storage Disease type 5 presenting in a person at an age of 73 years . Felice and colleagues and Pourmand and colleagues also have documented late presentations of Glycogen Storage Disease type 5 cases. This suggests that doctors should have clinical suspicion irrespective of the age of presentation  .
PYGM gene is involved in the production of an enzyme called myophosphorylase. This enzyme is only found in muscle cells and is responsible for the breakdown of glycogen to the final product glucose for use in muscles. In the muscles, myophosphorylase breaks down glycogen into glucose-1-phosphate which is a simple form of sugar. This is then converted to glucose. Glucose is the main energy source for most cells of the body.
Glycogen Storage Disease type 5 is caused due to mutations in this PYGM gene which cause deficiency of myophosphorylase. This affects the conversion of glycogen to glucose in the muscles. Thus, the muscle cells do not have enough energy production which leads to easy muscle fatigue and other symptoms of Glycogen Storage Disease type 5. The severity of the symptoms is dependent on the degree of deficiency of myophosphorylase.
Glycogen Storage Disease type 5 patients have difficulty performing exercises of any kind because the body is deficient in the normal source of energy (glucose) and instead the body may break down its own muscles. The breakdown of muscles can release a protein called myoglobin in the blood which produces dark red urine. If excess myoglobin is released on intense exercises then it overburdens the kidneys causing acute kidney failure.
Being an inherited genetic defect, the only way the disease might manifest in an offspring is if it received two defective copies of the mutated gene, one from each parent. Amniocentesis might be done during pregnancy to do a DNA analysis of the embryo. Once born, there is no way to prevent or reverse the condition.
Glycogen storage disease Type 5 (McArdle Disease or GSD-V) is one among the many in a group of inherited glycogen storage diseases. Specific enzymes catalyse reactions which help convert glycogen to glucose. Many different mutations have been reported for each type of Glycogen Storage Disease .
The deficiency of these enzymes causes glycogen accumulation in tissues. It can cause systemic outcomes or specific tissue related outcomes . Glycogen Storage Disease Type 5 is an inherited autosomal recessive disease.
In Glycogen Storage Disease Type 5, the deficient enzyme is myophosphorylase . This is required for the breakdown of stored glycogen to glucose in the muscles. The disease was first reported in 1951 by Dr. Brian McArdle of Guy's Hospital, London. Glycogen Storage Disease Type 5 has two autosomal recessive forms, a childhood-onset form and an adult-onset form.
Glycogen Storage Disease type 5 is a genetic disorder. It is caused due to deficiency of enzyme myophosphorylase. Most people with Glycogen Storage Disease type 5 may suffer from it since childhood but it goes undiagnosed till adulthood. People with Glycogen Storage Disease type 5 appear physically healthy but suffer from fatigue post exercises. This can be confused with being not fit or disinclined to exercise. Hence, symptoms of Glycogen Storage Disease type 5 are usually detected in the second or third decade of life.
Myophosphorylase found in muscles when deficient causes muscle cramps, pain and stiffness. Fatigue, pain and weakness with strenuous activities like jogging, swimming or even walking are the characteristic symptoms of the disease.
Since deficiency of myophosphorylase affects conversion of glycogen to glucose, the muscles lack enough energy (glucose) for strenuous physical activities. Thus these patients experience easy tiredness, cramps, pain and soreness. 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 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 much abnormal findings. Tests advised include creatine kinase testing, urine analysis, ischemic forearm test and muscle biopsy. Biochemical assay is a confirmatory test for the enzyme activity.
Always remember to mention your disease whenever you visit any medical setup. A balanced diet rich in protein and vitamins aids to improve muscle tolerance.Glycogen Storage Disease type 5 patients must avoid strenuous exercises. Though they must continue light exercises and stretches to improve the muscle strength and flexibility. Be aware of your disease, your energy levels and your general state of health. People with Glycogen Storage Disease type 5 can lead an active life as long as you do not over do the workouts and maintain a healthy routine.