Fatal infantile cytochrome c oxidase deficiency: decrease of immunologically detectable enzyme in muscle.
A 2-month-old boy had progressive generalized weakness, hypotonia, and respiratory insufficiency requiring assisted ventilation. At age 3 1/2 months, he started having seizures and recurrent pulmonary infections; he died at age 7 months. Serum lactate was chronically elevated, but there was no aminoaciduria. Histochemical and ultrastructural studies of muscle biopsies at ages 2 and 3 months showed excessive mitochondria, lipid, and glycogen; a third biopsy at 6 months showed marked increase in perimysial fibrous and fat tissue. Cytochrome c oxidase activity was 7% of normal in the first biopsy and undetectable in the others. Cytochrome spectra of mitochondria isolated from postmortem muscle showed complete lack of cytochrome aa3. Antibodies were obtained against cytochrome c oxidase purified from normal human heart. Immunotitration and enzyme-linked immunosorbent assay (ELISA) showed decreased immunologically reactive enzyme protein in the patient's muscle, but SDS-PAGE electrophoresis of immunoprecipitates of muscle mitochondrial extracts showed the presence of all cytochrome c oxidase subunits. These data suggest that decreased synthesis of one or more subunits may result in markedly decreased concentration of electrophoretically normal complex IV in skeletal muscle.
Bresolin
N
N
Zeviani
M
M
Bonilla
E
E
Miller
R H
RH
Leech
R W
RW
Shanske
S
S
Nakagawa
M
M
DiMauro
S
S
D030401:Cytochrome-c Oxidase Deficiency; D003576:Electron Transport Complex IV / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007158:Immunologic Techniques; D007223:Infant; D007668:Kidney / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D009132:Muscles / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D009206:Myocardium / Q000201:enzymology
D003576:Electron Transport Complex IV