Other myopathic conditions may mimic metabolic myopathies, in particular the limb–girdle muscular dystrophies or, more commonly, chronic inflammatory myopathies such as polymyositis. For a more detailed discussion, Wortmann and DiMauro provide an excellent review of the subject.1 In general, other systemic features such as rash, malaise, interstitial fibrosis, carditis, and gastrointestinal dysfunction should suggest the presence of an acquired inflammatory myopathy, but the distinction can be difficult.
Many tools are available to the clinician to aid in the diagnostic evaluation of metabolic myopathies. One of the most cost-effective and least invasive tools remains the clinical history and physical examination, which can provide invaluable information that allows the clinician to narrow or broaden further diagnostic testing as appropriate and potentially avoid unnecessary invasive testing. A thorough history and examination will often help differentiate a dynamic myopathy characterized by transient, severe symptoms from a static myopathy characterized by fixed weakness. Because the primary metabolic myopathies are hereditary, a thorough, targeted family history may provide valuable information. Routine tests including serum electrolytes, glucose, liver transaminases, creatine kinase (CK), lactate, ammonia, and urinalysis may be useful. In some cases, the forearm exercise test, electromyography (EMG), and routine muscle biopsy may provide valuable information (see Table 1, p. 16, and Table 3, p. 23). Diagnostic tests such as urine organic acids, plasma amino acids, and plasma acylcarnitine profile may provide more specific results, allowing the clinician to approach more costly confirmatory testing, including enzyme and DNA analysis on leukocytes, fibroblasts, and the liver, in a rational, cost-effective manner (see Table 3, p. 23).
As a group, the metabolic myopathies are often broadly divided into three categories based on the underlying metabolic defect: 1) muscle glycogenoses, 2) disorders of FAO, and 3) mitochondrial myopathies. The following discussion will focus on the most common primary metabolic myopathies associated with primarily dynamic symptoms characterized by exercise-induced myalgia, early fatigue, cramping, and myoglobinuria.
Disorders of Glycogen Metabolism (Muscle Glycogenoses)
The classification of GSDs is based on the associated enzyme defect and clinical presentation.5 Two GSDs do not involve skeletal muscle: GSD type I (von Gierke disease) and GSD type VI (Hers disease). Some GSDs produce primarily static symptoms of fixed, proximal weakness, including GSD type II (Pompe disease), GSD type III (Cori-Forbes disease), and GSD type IV (Andersen disease). The latter two disorders are typified by liver involvement and will not be further discussed. Late-onset Pompe disease causes progressive, proximal muscle weakness that may progress to respiratory failure, and it falls into the static myopathy category.
