Full text with diagnostic algorithm at:
Curr Neurol Neurosci Rep. 2010 Mar; 10(2): 118–126.
A Diagnostic Algorithm for Metabolic Myopathies
Andres Berardo, Salvatore DiMauro, and Michio Hiranocorresponding author
Department of Neurology, Columbia University Medical Center, 630 West 168th Street, P&S 4-423, New York, NY 10032, USA
Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1).
From a clinical point of view, metabolic myopathies can be categorized into two different groups: 1) those that show symptoms and signs related to exercise (exercise intolerance, cramps, myalgias, myoglobinuria) with normal interictal examination and 2) those with fixed symptoms, such as muscle weakness, often associated with systemic involvement (eg, endocrinopathies or encephalopathies). When evaluating a patient with exercise-related symptoms, we should ask two questions: 1) What type of exercise provokes symptoms? 2) Are there associated triggering factors? If short bursts of high-intensity exercise trigger muscle cramps or pigmenturia, the patient may have a defect of glycogen metabolism . Examples of this type of activity include weight lifting and sprinting. In the United States and other countries where baseball is popular, the “home run” (Haller) sign—that is, the inability to sprint around the bases because of exercise-induced muscle spasms—is a typical complaint in young patients with glycogenoses, such as McArdle disease (Dr. Ronald Haller, personal communication). In contrast, if the patient reports that prolonged exercise (eg, hiking or playing soccer) triggers myalgias, fatigue, and pigmenturia without acute contractures, he or she likely has a defect of fatty acid oxidation. The symptoms often occur when the patient is fasting. A prototypical example is a young adult with CPT II deficiency who enlists in military service and has difficulty completing long marches because of fatigue and myalgias followed by pigmenturia. Some patients with glycolytic or lipid disorders may develop progressive myopathy and persistent weakness. Patients with mitochondrial diseases may show a wide range of manifestations that are exercise induced, fixed, or both, but exercise intolerance is particularly common and manifests as the inability to perform activities because of premature fatigue out of proportion to weakness. This article briefly goes through general clinical aspects of these metabolic myopathies, emphasizing the more common forms (Table 1), and provides an algorithm for diagnosing these diverse conditions (Fig. 1).