What is Metabolic Myopathies?

Metabolic myopathies are a group of disorders, each caused by a different genetic defect that interfere with chemical reactions (metabolism) involved in turning food to energy. As muscles require a lot of energy to work properly, when energy levels are too low or unused fuel molecules build up inside muscle cells, muscle weakness and exercise intolerance with muscle pain or cramps may occur.


Signs and symptoms vary among different types of metabolic myopathies, depending on which metabolic enzyme is defective. Symptoms include:
  • Exercise intolerance
  • Muscle weakness
  • Muscle cramping
  • Heart problems
  • Difficulty breathing if the disease affects muscles involved in respiration
  • Rhabdomyolysis: a breakdown of muscle tissue that can cause kidney damage

Causes and Inheritance

Metabolism is the process of converting fuel sources (such as sugar) into stable energy inside the cells, which requires the proper functioning of many enzymes. Metabolic myopathies occur when genetic mutations cause insufficient levels of a particular enzyme used in the process. When this happens, the affected muscles cannot covert fuel into energy and this cannot function. For example, Pompe Disease results from a genetic defect in acid maltase, or acid alpha-glucosidase (GAA). Normally, the body uses the GAA enzyme to breaks down glycogen (stored sugar) into glucose, which is used to fuel cells. In Pompe Disease, mutations in the GAA gene reduce or completely eliminate this enzyme.

Most of the metabolic myopathies are inherited in an autosomal recessive pattern, required two defective copies of the gene to have the disease, such as Pompe Disease (acid maltase deficiency). Other metabolic myopathies can be inherited in an X-linked recessive pattern (such as phosphoglycerate kinase deficiency), or an autosomal dominant pattern (such as carnitine palmityl transferase deficiency).


Metabolic myopathies share similar symptoms to many other conditions. In addition to personal and family history evaluation, and physical exams, specialized tests may be used. A muscle biopsy can determine the cause of muscle weakness. Electromyography (EMG) may be used to rule out muscular dystrophies and other disorders. A blood test can detect signs of muscle tissue breakdown, and may be conducted in conjunction with intense or moderate exercise. Genetics tests are available for many of the genetic mutations underlying various metabolic myopathies.

Management and Treatment

People with metabolic myopathies must avoid acute muscle breakdowns that release muscle proteins into the bloodstream and cause severe kidney damage, often triggered by overexertion. Doctors and other members of the care team may help to develop a plan for managing physical activities. Some types of metabolic myopathies can weaken heart or respiratory muscles, which should be monitored regularly by a specialist. Diet modification, such as a high-protein or low-fat diet, may be helpful, depending on which enzyme(s) are affected by a metabolic myopathy, People with metabolic muscle disorders may be at higher risk for a potentially fatal reaction to certain common general anesthetics. This reaction, called malignant hyperthermia, can be avoided in planned surgeries by using lower-risk anesthetics. For Pompe Disease, enzyme replacement therapy is available since the FDA approval of two drugs: Myozyme and Lumizyme. Both are synthetic forms of the acid maltase enzyme.