McArdle disease is caused by mutations in the PYGM gene.
Understanding McArdle Disease and the PYGM Gene
McArdle disease, also known as glycogen storage disease type V (GSD V), is a genetic metabolic disorder affecting skeletal muscles. This condition results from a deficiency in the muscle isoform of glycogen phosphorylase, an enzyme crucial for breaking down glycogen (stored glucose) into glucose-1-phosphate, which the muscle can use for energy during physical activity.
The PYGM gene provides the instructions for making this muscle glycogen phosphorylase enzyme. Therefore, when this gene is mutated, the enzyme is either deficient or completely absent.
Consequences of PYGM Gene Mutations
Mutations in the PYGM gene lead to the following:
- Impaired Glycogen Breakdown: The body cannot efficiently break down glycogen in muscle tissue.
- Energy Deprivation: Muscles are starved of energy during exercise.
- Symptoms: Patients with McArdle disease experience symptoms such as muscle cramps, pain, fatigue, and sometimes muscle breakdown (rhabdomyolysis) during physical exertion.
Genetic Inheritance
McArdle disease is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated PYGM gene (one from each parent) to develop the condition. People who inherit only one copy of the mutated gene are carriers and usually do not exhibit symptoms.
Diagnosis and Management
Diagnosis typically involves blood tests to measure creatine kinase levels (which are elevated after exercise in individuals with McArdle disease) and muscle biopsies to assess glycogen phosphorylase activity. Genetic testing can confirm the presence of PYGM gene mutations. Management strategies involve modifying exercise routines to avoid strenuous activity, dietary adjustments, and in some cases, supplementation with creatine or other substances to improve exercise tolerance.
