Despite the demonstration of a clear biochemical defect, the genetic alterations causing childhood forms of
cytochrome c oxidase (
COX) deficiency remain unknown. The double genetic origin (nuclear and
mitochondrial DNA), and the complexity of COX
enzyme structure and regulation, indicate the need for genetic investigations of the molecular structure of individual COX subunits. In the present study a new
monoclonal antibody, which reacts exclusively with heart-type human COX subunit VIIa (VIIa-H), and other
monoclonal antibodies against human COX subunits, were used in the immunohistochemical analysis of skeletal muscle from children with different forms of
mitochondrial myopathy with
COX deficiency. By immunohistochemical investigation a normal reaction was seen with
antibodies to COX subunits IV, Va+Vb, and VIa+VIc in all four cases, and in two cases with
antibodies to COX VIIa-H and VIIa+VIIb. In muscle from a fatal infantile case with cardiac and skeletal muscle involvement, no immunohistochemical reaction was seen with the
monoclonal antibody against the tissue-specific subunit VIIa-H. In muscle from an 11-year-old boy with exclusive muscular symptoms and signs, immunohistological reactions were absent with COX subunit VIIa-H and COX subunits VIIa+VIIb, and slightly decreased with COX subunit II, thus demonstrating a different molecular mechanism in each case. It is concluded that the molecular basis of
COX deficiency in childhood may vary greatly between patients.