Clinical Information

Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which leads to leakage of potentially toxic cellular contents into the blood stream. The clinical severity can range from asymptomatic creatine kinase elevation to a life-threatening disease. The clinical features include acute-onset myalgia, transient muscle weakness, and pigmenturia. Genetic causes of rhabdomyolysis include metabolic myopathy, mitochondrial disorders, disorders of intramuscular calcium release, and muscular dystrophies.

Metabolic myopathies are a diverse group of inherited biochemical diseases involving limitation of the use of fuels by skeletal muscle to generate energy. Metabolic myopathies include disorders of fatty acid oxidation, disorders of glycogen and glucase metabolism, and mitochondrial respiratory chain disease. Biochemical testing in multiple tissue types, including blood, urine, and muscle, can help to determine which category of muscle disease is most likely.

Disorders of fatty acid oxidation are one category of metabolic myopathies characterized by hypoketotic hypoglycemia, hepatic dysfunction, skeletal myopathy, dilated and hypertrophic cardiomyopathy, and sudden or unexpected death. Mitochondrial fatty acid beta-oxidation plays an important role in energy production, particularly in skeletal and heart muscle, and in hepatic ketone body formation during periods of fasting. Biochemical testing such as urine organic acids, plasma acylcarnitines, and fatty acids can aid in diagnosis. These test results are influenced by dietary factors and the clinical status of the patient, which often leads to incomplete diagnostic information or even false-negative results.

Disorders of glycogen and glucose metabolism are another category of metabolic myopathies primarily affecting muscle and resulting in exercise intolerance, recurrent rhabdomyolysis, and myoglobinuria. Creatine kinase level is typically elevated during a major event. Muscle biopsy is often performed to verify absence of enzyme activity for the specific type of glycogenosis disease.

Polyglucosan body disease involves progressive neurogenic bladder, spasticity and weakness causing gait difficulties from either primary muscle or nerve involvements, sensory loss mainly in the distal lower extremities, and mild cognitive difficulties such as executive dysfunction. Mitochondrial myopathies due to coenzyme Q10 deficiency are a group of heterogenous diseases. These mitochondrial diseases are characterized by muscle weakness, exercise intolerance, elevated creatine kinase, and abnormal muscle biopsy findings.