Differential diagnosis of fatal and benign cytochrome c oxidase-deficient myopathies of infancy: an immunohistochemical approach.

To differentiate the 2 major myopathies of infancy due to cytochrome c oxidase (COX) deficiency, we studied muscle biopsies from 4 patients with fatal myopathy and 4 with benign myopathy using biochemical, histochemical, and immunohistochemical techniques. Immunohistochemistry with antibodies directed against individual subunits of COX differentiated the 2 phenotypes: the fatal infantile myopathy was characterized by absence of the nuclear DNA (nDNA)-encoded subunit VIIa,b of COX, while in the benign myopathy both VIIa,b and the mitochondrial DNA (mtDNA)-encoded subunit II were absent. Early differential diagnosis between fatal and benign COX-deficient myopathies is of critical importance for prognosis and management of these infants, because the benign form is initially life-threatening but ultimately reversible.