Metabolic Myopathies

Mark A. Tarnopolsky, MD, PhD, FRCP Muscle and Neuromuscular Junction Disorders p. 1752-1777 December 2022, Vol.28, No.6 doi: 10.1212/CON.0000000000001182
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PURPOSE OF REVIEW Metabolic myopathies are disorders that affect skeletal muscle substrate oxidation. Although some drugs and hormones can affect metabolism in skeletal muscle, this review will focus on the genetic metabolic myopathies.

RECENT FINDINGS Impairments in glycogenolysis/glycolysis (glycogen storage disease), fatty acid transport/oxidation (fatty acid oxidation defects), and mitochondrial metabolism (mitochondrial myopathies) represent most metabolic myopathies; however, they often overlap clinically with structural genetic myopathies, referred to as pseudometabolic myopathies. Although metabolic myopathies can present in the neonatal period with hypotonia, hypoglycemia, and encephalopathy, most cases present clinically in children or young adults with exercise intolerance, rhabdomyolysis, and weakness. In general, the glycogen storage diseases manifest during brief bouts of high-intensity exercise; in contrast, fatty acid oxidation defects and mitochondrial myopathies usually manifest during longer-duration endurance-type activities, often with fasting or other metabolic stressors (eg, surgery, fever). The neurologic examination is often normal between events (except in the pseudometabolic myopathies) and evaluation requires one or more of the following tests: exercise stress testing, blood (eg, creatine kinase, acylcarnitine profile, lactate, amino acids), urine (eg, organic acids, myoglobin), muscle biopsy (eg, histology, ultrastructure, enzyme testing), and targeted (specific gene) or untargeted (myopathy panels) genetic tests.

SUMMARY Definitive identification of a specific metabolic myopathy often leads to specific interventions, including lifestyle, exercise, and nutritional modifications; cofactor treatments; accurate genetic counseling; avoidance of specific triggers; and rapid treatment of rhabdomyolysis.

Address correspondence to Dr Mark Tarnopolsky, McMaster Children’s Hospital, 1200 Main St W, Rm 2H26, Hamilton, ON, Canada L8N 3Z5, [email protected].

RELATIONSHIP DISCLOSURE: Dr Tarnopolsky has received personal compensation in the range of $500 to $4999 for serving as a consultant for Alexion Pharmaceuticals, for serving on a scientific advisory or data safety monitoring board for Reneo Pharmaceuticals, and for serving on a speakers bureau for Sanofi; in the range of $5000 to $9999 for serving as a consultant for Sanofi; and in the range of $10,000 to $49,999 for serving as a consultant for Reneo Pharmaceuticals. Dr Tarnopolsky holds stock in Cloud DX and Synaptive Medical. The institution of Dr Tarnopolsky has received research support from the Canadian Institutes of Health Research. Dr Tarnopolsky has received intellectual property interests from a discovery or technology relating to health care.


© 2022 American Academy of Neurology.