Related Experiment Videos
Cytochrome c oxidase deficiency in infancy
A Oldfors1, H Sommerland, E Holme
1Department of Pathology, Gotenburg University, Sahlgren's Hospital, Sweden.
Insights
This study investigated cytochrome c oxidase deficiency in children with muscle weakness. Four out of five patients confirmed to have this deficiency showed mitochondrial abnormalities, impacting respiratory chain function.
Area of Science:
- Biochemistry
- Mitochondrial Biology
- Pediatric Neurology
Background:
- Early-onset muscle weakness and lactic acidosis can indicate mitochondrial dysfunction.
- Cytochrome c oxidase (COX) deficiency is a key indicator of respiratory chain defects.
Observation:
- Five children presented with muscle weakness, lactic acidosis, and reduced COX staining.
- Oximetric assays confirmed COX deficiency in four patients, with one showing reduced activity.
- Muscle biopsies revealed mitochondrial structural abnormalities and lipid storage in confirmed COX deficiency cases.
Findings:
- COX deficiency was confirmed oximetrically in four patients.
- Histochemical analysis showed variable COX deficiency in muscle fibers, with some exceptions.
- Ultrastructural examination highlighted mitochondrial heterogeneity and enzyme deficiency in abnormal mitochondria.
Implications:
- This research clarifies diagnostic criteria for COX deficiency in pediatric mitochondrial diseases.
- Understanding COX deficiency heterogeneity is crucial for accurate diagnosis and potential therapeutic strategies.
- Further research into the genetic basis of COX deficiency is warranted.
Abstract:
Five children with early onset of muscle weakness, lactic acidosis and deficient cytochrome c oxidase staining in the muscle biopsy were studied. By oximetric assay of the respiratory chain of isolated mitochondria, cytochrome c oxidase deficiency was confirmed in four of the cases, while one case showed only a slight decrease of cytochrome c oxidase activity but considerably reduced activity when assayed spectrophotometrically. The muscle biopsies exhibited mitochondrial structural abnormalities and lipid storage in the four cases with oximetrically confirmed cytochrome c oxidase deficiency, while the biopsy of the case with markedly reduced activity of cytochrome c oxidase only in the enzyme-histochemical and spectrophotometrical assays had normal morphology. The light microscopical staining of cytochrome c oxidase in the four cases with oximetrically confirmed deficiency showed deficient staining of the enzyme in all extrafusal fibres in three cases but one of the cases had normal enzyme-histochemical activity of cytochrome c oxidase in about 25% of the fibres. In two cases muscle spindles were included in the biopsy. The intrafusal fibres showed normal enzyme-histochemical activity of cytochrome c oxidase. Ultrastructural examination of the enzyme distribution in two of the cases revealed great heterogeneity of the mitochondria. The structurally abnormal mitochondria were usually deficient of enzyme activity. The mitochondria of endothelial cells appeared to have normal activity. Immunohistochemical staining with polyclonal antibodies to cytochrome c oxidase revealed presence of immunoreactive material corresponding to the localisation of mitochondria in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)