Volume 51, Number 3

Myopathic Diseases

Robert L. Wortmann, MD
Department of Internal Medicine
University of Oklahoma College of Medicine
Tulsa, OK

Some metabolic myopathies are primary and the result of known biochemical defects that alter the muscle’s ability to maintain adequate levels of ATP. These can be attributed to defects in glycogen, lipid, or mitochondrial metabolism. Others are secondary and caused by various endocrine disorders, electrolyte abnormalities, or drug toxicities.

To date, 11 different diseases caused by an underlying defect in glycogen synthesis, glycogenolysis, or glycolysis have been identified (8). These are often referred to as the glycogen storage diseases (GSD), because of the glycogen that accumulates in muscle as a consequence of the defect. McArdle’s disease, myophosphporylase deficiency, is the prototypic GSD. It has three potential presentations, together representing the spectrum of GSD symptomatology. Symptoms may begin during childhood with easy fatigue, but significant problems including exercise intolerance with severe muscle cramping, rhabdomyolysis, and myoglobinura may not develop until adolescence or adulthood. A subset of adults (as old as age 78 years) presents with progressive proximal muscle weakness with no history of cramps or myoglobinuria.

The other more common GSDs are phosphofructokinase deficiency and acid maltase deficiency. Patients with a GSD may be difficult to differentiate from those with an IIM because most GSD patients have elevated CPK levels even when symptom-free, and their EMGs reveal evidence of myopathy. Thus, they fulfill three of the four criteria for polymyositis. Muscle biopsy is needed to differentiate among these conditions and to make the correct diagnoses.

A variety of disorders of fatty acid and mitochondrial metabolism also can cause myopathy. The former are referred to as lipid storage diseases (LSD) and the latter termed mitochondrial myopathies (9). The clinical spectrum of these diseases is quite diverse and includes progressive muscle weakness as well as exercise intolerance with rhabdomyolysis and myoglobinuria.

Knowledge of the specific defect does not allow prediction of the clinical presentation. For example, a deficiency of carnitine -- an essential intermediate necessary for the transport of long-chain fatty acids into mitochondria -- causes lipid deposition in muscle a disease easily confused with polymyositis. These individuals have proximal muscle weakness, elevated CPK levels and myopathic EMG findings. In contrast, a deficiency of carnitine palmitoyltransferase (CPT), the enzyme that catalyzes the transport of the long-chain fatty acid-carnitine complex into mitochondria, cause sporadic attacks of myalgia and myoglobinuria. Serum CPK levels, EMGs, and muscle histology are normal except with attacks. Mitochondrial myopathies may cause each presentation but are more often associated with progressive external ophthalmoplegia, other neurologic findings, or multisystem disease.