IMMUNOHISTOCHEMICAL ANALYSIS OF MUSCLE CYTOCHROME-C-OXIDASE DEFICIENCY IN CHILDREN

Despite the demonstration of a clear biochemical defect, the genetic a lterations causing childhood forms of cytochrome c oxidase (COX) defic iency remain unknown. The double genetic origin (nuclear and mitochond rial DNA), and the complexity of COX enzyme structure and regulation, indicate the need for genetic investigations of the molecular structur e of individual COX subunits. In the present study a new monoclonal an tibody, which reacts exclusively with heart-type human COX subunit VII a (VIIa-H), and other monoclonal antibodies against human COX subunits , were used in the immunohistochemical analysis of skeletal muscle fro m children with different forms of mitochondrial myopathy with COX def iciency. By immunohistochemical investigation a normal reaction was se en 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. I n muscle from a fatal infantile case with cardiac and skeletal muscle involvement, no immunohistochemical reaction was seen with the monoclo nal antibody against the tissue-specific subunit VIIa-H. In muscle fro m an ii-year-old boy with exclusive muscular symptoms and signs, immun ohistological reactions were absent with COX subunit VIIa-H and COX su bunits VIIa+VIIb, and slightly decreased with COX subunit II, thus dem onstrating a different molecular mechanism in each case. It is conclud ed that the molecular basis of COX deficiency in childhood may vary gr eatly between patients.