Glycogen storage disease type V (GSD5, GSD-V), also known as McArdles disease, is a metabolic disorder, one of the metabolic myopathies, more specifically a muscle glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as one in 100,000, roughly the same as glycogen storage disease type I.The disease was first reported in 1951 by Dr. Brian McArdle of Guys Hospital, London. Signs and symptoms
The onset of this disease is usually noticed in childhood, but often not diagnosed until the third or fourth decade of life. Symptoms include exercise intolerance with muscle pain, early fatigue, painful cramps, inappropriate rapid heart rate response to exercise, and may include myoglobin in the urine (often provoked by a bout of exercise). "In McArdles, our heart rate tends to increase in what is called an inappropriate response. That is, after the start of exercise it increases much more quickly than would be expected in someone unaffected by McArdles." Myoglobinuria may be seen due to the breakdown of skeletal muscle known as rhabdomyolysis, a condition in which muscle cells breakdown, sending their contents into the bloodstream.
"Patients may present at emergency rooms with severe fixed contractures of the muscles and often severe pain. These require urgent assessment for rhabdomyolysis as in about 30% of cases this leads to acute kidney injury. Left untreated, this can be life-threatening. In a small number of cases compartment syndrome has developed, requiring prompt surgical referral. Genetics
"GSDV is inherited in an autosomal recessive manner. At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. "Two autosomal recessive forms of this disease occur, childhood-onset and adult-onset. The gene for myophosphorylase, PYGM (the muscle-type of the glycogen phosphorylase gene), is located on chromosome 11q13. According to the most recent publications, 95 different mutations have been reported. The forms of the mutations may vary between ethnic groups. For example, the R50X (Arg50Stop) mutation (previously referred to as R49X) is most common in North America and western Europe, and the Y84X mutation is most common among central Europeans.The exact method of protein disruption has been elucidated in certain mutations. For example, R138W is known to disrupt to pyridoxal phosphate binding site. In 2006, another mutation (c.13_14delCT) was discovered which may contribute to increased symptoms in addition to the common Arg50Stop mutation. Myophosphorylase
Structure
The myophosphorylase structure consists of 842 amino acids. Its molecular weight of the unprocessed precursor is 97 kDa. The three-dimensional structure has been determined for this protein.