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[Mitochondrial DNA deletion in hereditary cardio-encephalo-myopathy]
Insights
This study reports a rare cardio-encephalo-myopathy in siblings, characterized by severe mitochondrial dysfunction in muscle and brain tissues. Genetic analysis revealed coexisting normal and deleted mitochondrial DNA, explaining the molecular basis of this fatal condition.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Presents a case study of a female infant with cardio-encephalo-myopathy, a severe inherited condition.
- The patient experienced multiple affected siblings, suggesting a genetic etiology.
Observation:
- Autopsy revealed significantly reduced mitochondrial enzyme activity, particularly carnitine acetyltransferase, in skeletal muscle.
- Electron microscopy showed severe mitochondrial structural abnormalities in cardiac and muscle tissues.
- Cerebellar Purkinje cells were reduced in number and exhibited abnormal mitochondrial structures.
Findings:
- Muscle tissue displayed marked deficiencies in key mitochondrial enzymes including carnitine acetyltransferase, cytochrome oxidase, NADH cytochrome C oxidoreductase, and citrate synthase.
- Abnormal mitochondrial morphology was prevalent in cardiac and skeletal muscle, as well as Purkinje cells.
- Molecular analysis identified the coexistence of normal and deleted mitochondrial DNA within affected tissues.
Implications:
- The findings suggest a novel mitochondrial disorder with significant impact on cardiac, neurological, and muscular systems.
- Coexisting normal and deleted mitochondrial DNA provides a molecular explanation for the observed multi-systemic defects.
- This case highlights the importance of investigating mitochondrial DNA integrity in unexplained pediatric myopathies and encephalopathies.
Abstract:
The case of a female patient with cardio-encephalo-myopathy who died of her illness at one year of age, similarly to her three sisters, is reported. In autopsy samples, like muscle, heart, liver and cerebellum activities of several mitochondrial enzymes were determined. In the skeletal muscle serious decrease of carnitine acetyltransferase was observed (from the normal 4.8 U/g to 0.08 U/g wet weight), while in other tissues this activity was normal. In the muscle activities of several other mitochondrial enzymes were also decreased (cytochrome oxidase, NADH cytochrome C oxidoreductase, citrate synthase), while in other tissues there were no similar changes. Serious distortion was observed in the structure of the majority of mitochondria of muscle and heart by electronmicroscopy. The number of the Purkinje-cells in the cerebellum decreased, and the cells were shrunken, their axons were fragmented and disoriented. Also the structure of the mitochondria was abnormal in the Purkinje-cells, while it was normal in other areas of the cerebrum. In te tissues of the patient normal and deleted mitochondrial DNA coexisted as which could explain the genetic background of this disease at molecular level.