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Fatal infantile mitochondrial myopathy due to cytochrome c oxidase deficiency
Insights
Cytochrome c oxidase deficiency, a severe mitochondrial disease, caused progressive muscle weakness and respiratory failure in an infant. This case highlights the critical role of this enzyme in cellular energy production.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Mitochondrial respiratory chain defects are a significant cause of inherited metabolic disorders.
- Cytochrome c oxidase (COX) is a crucial enzyme complex in the mitochondrial electron transport chain, essential for ATP production.
Observation:
- A case study of an infant presenting with failure to thrive, hypotonia, and progressive weakness.
- Clinical deterioration led to respiratory arrest and death at 14 weeks of age.
- Biochemical analysis revealed lactic acidosis and generalized aminoaciduria.
Findings:
- Muscle biopsy demonstrated a complete absence of cytochrome c oxidase activity (<5% of controls).
- Spectroscopic analysis of muscle mitochondria confirmed the absence of cytochrome aa3 and a partial deficiency of cytochrome b.
- Ultrastructural examination revealed abnormal mitochondria with reduced cristae and an altered matrix.
Implications:
- This case underscores the severe consequences of cytochrome c oxidase deficiency, primarily impacting skeletal muscle and leading to fatal outcomes.
- The findings suggest autosomal recessive inheritance, providing crucial information for genetic counseling and further research into COX deficiency.
- Understanding the biochemical and ultrastructural defects is vital for potential therapeutic strategies in mitochondrial diseases.
Abstract:
A case of cytochrome c oxidase deficiency primarily affecting skeletal muscle is described. The child was admitted at 4 weeks due to failure to thrive and examination at that time revealed weakness and hypotonia. His condition deteriorated until at 11 weeks respiratory arrest necessitated artificial ventilation and death occurred at 14 weeks. Biochemical investigation showed lactic acidaemia and generalised aminoaciduria. Histochemical examination of muscle obtained at biopsy showed strong reactions for some oxidative enzymes, but by contrast cytochrome c oxidase could not be detected. Cytochrome c oxidase activity was less than 5% of control values in an extract of fresh muscle. The reduced-minus oxidised absorption spectra of muscle mitochondrial fractions prepared from post-mortem tissue showed an absence of cytochrome aa3 and a partial deficiency of cytochrome b. Ultra-structural examination showed abnormal mitochondria with loss of cristae and an abnormal granular matrix. The family history suggests autosomal recessive inheritance.