Succinate dehydrogenase deficiency - A qualitative and quantitative assessment in muscle

Background.-Partial succinate dehydrogenase deficiency (15% to 50% of norma l reference enzyme activity) in skeletal muscle causes mitochondrial myopat hy with various symptoms, for example, brain involvement, cardiomyopathy, a nd/or exercise intolerance. The deficiency may be isolated or may coexist w ith other respiratory-chain enzyme defects. The histopathologic assessment of succinate dehydrogenase activity in muscle biopsies of patients with sus pected mitochondrial myopathies has focused on the finding of increased sta ining, usually in ragged-red fibers, rather than on reduced staining. Objectives.-To determine the prevalence of muscle succinate dehydrogenase d eficiency among patients with respiratory-chain defects and to determine wh ether the reduced activity is present histochemically and is comparable to the quantitative reduction found in muscle homogenates. Patients and Methods.-One hundred eight muscle biopsies were evaluated from patients with suspected mitochondrial myopathies by qualitative histochemi cal analysis and quantitative biochemical analyses of respiratory-chain enz ymes using standard methodologies. Results.-Fifty-two patients had defects in respiratory chain complexes; of these patients, 12 (23%) had partial deficiencies in succinate dehydrogenas e activity either alone or together with reductions in other enzymes. The r educed activity was detectable histochemically in muscle biopsies with resi dual enzyme activity of up to 34% of the normal reference activity, while 2 biopsies with higher residual activity (49% and 68% of normal) could not b e distinguished from normal biopsies. Conclusions-Of the patients with respiratory-chain enzyme defects, 23% had partial deficiencies of succinate dehydrogenase activity in muscle biopsies . This reduction could be detected histochemically in biopsies in most case s. The marked prevalence of succinate dehydrogenase deficiency among patien ts with respiratory-chain defects and its detection initially by histochemi cal analysis are important findings.