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Vascular involvement in benign infantile mitochondrial myopathy caused by reversible cytochrome c oxidase deficiency
Insights
This study shows that a rare mitochondrial disease causing severe weakness in infants can improve over time. Abnormal mitochondria in muscles and blood vessels normalized, leading to a full recovery in a young girl.
Area of Science:
- Mitochondrial Medicine
- Pediatric Neurology
- Biochemistry
Background:
- Mitochondrial disorders, particularly those affecting cytochrome c oxidase (COX), can present with severe neonatal symptoms including profound weakness and lactic acidosis.
- Early diagnosis and monitoring are crucial for understanding the natural history and potential for recovery in these complex conditions.
Observation:
- A 1-month-old infant exhibited severe hypotonia, weakness, and lactic acidosis, alongside ragged-red fibers and significantly reduced COX activity in muscle tissue.
- Electron microscopy revealed abnormal mitochondria in skeletal muscle fibers and, notably, in the vascular system, including endothelial and smooth muscle cells of small arteries.
Findings:
- Biochemical analysis confirmed an isolated COX deficiency (16% of control levels) at 11 weeks of age.
- Remarkably, at 44 months, COX activity normalized, and electron microscopy showed the disappearance of abnormal mitochondria in both muscle and vascular tissues.
- The patient demonstrated significant clinical improvement, achieving developmental milestones and showing no muscle weakness by age 5.
Implications:
- This case highlights the potential for reversibility of mitochondrial abnormalities, including vascular involvement, in certain COX deficiencies.
- It suggests that some mitochondrial diseases may have a more benign and self-limiting course than previously thought, with implications for long-term prognosis and therapeutic strategies.
Abstract:
A 1-month-old Japanese girl had profound generalized weakness, hypotonia, and severe lactic acidosis. The infant improved gradually: she held her head at 9 months, learned to walk by 15 months. At the first muscle biopsy at 11 weeks of age, the specimen was characterized by numerous ragged-red fibers and decreased enzyme activity on cytochrome c oxidase (COX) staining. Electron microscopic findings were characterized by the presence of excessive abnormal mitochondria not only in skeletal muscle fibers but also in blood vessels. Vascular abnormalities consisted of an increased number of enlarged mitochondria in endothelial and smooth muscle cells of small arteries. Biochemical analysis showed an isolated defect of COX activity, which was only 16% of the mean control level. At the second biopsy at 44 months of age, the COX activity had increased to normal in the entire specimen. On electron microscopy, the abnormal mitochondria present on the first biopsy specimen had disappeared both in muscle fibers and blood vessels; nearly all mitochondria were morphologically normal at the second biopsy. Now at 5 years of age she can run and does not show muscle weakness. We report reversibility of abnormal mitochondria with age not only in skeletal muscle fibers but also in blood vessels in a patient, who had reversible COX deficiency with a benign clinical course.