Episodic weakness associated with exertional lactic acidosis and myopathy in Old English sheepdog littermates.

Two Old English Sheepdog littermates were evaluated for weakness that developed during periods of minimally intense exercise. Lactic acidosis accompanied by increased muscle enzyme activity, an increased lactate/pyruvate ratio, and increased venous PO2 supported the possibility of defective mitochondrial oxygen use. Electromyographic abnormalities included increased insertional activity and complex repetitive discharges. Muscle alterations included scattered myofiber necrosis, abundant endomysial connective tissue, excessive glycogen accumulation, and greater than normal numbers and vacuolation of mitochondria. A distinctive pattern of subsarcolemmal mitochondrial aggregates, referred to as "ragged red fibers" in human mitochondrial myopathies, was observed in muscle biopsy samples from 1 dog. Several features of the disease in these dogs, including onset of weakness during early life, simultaneous disease in littermates, subtle nonprogressive weakness of at least 3 years' duration, and partial reversibility of lactic acidosis following rest were suggestive of an inborn error of metabolism, consistent with mitochondrial myopathy.