Myopathy with ragged red fibers
Mitochondrial Myopathy
Clinical Features
The characteristic signs of a mitochondrial myopathy are the typical ragged red fibers in muscle. Some patients present with and isolated myopathy, in others the phenotype might be complicated with different neurological symptoms and a less favourable prognosis. Biochemical analysis of the muscle biopsy is a helpful tool to direct further genetic diagnostics.
Genetic Information
Mutations in different mtDNA genes (tRNA, mtCOI-III, ND genes) can underly the clinical symptoms. In patients with an isolated myopathy, the mutation is usually sporadic and only present in muscle and not in other tissues. In patients with a wider presentation of clinical symptoms (encephalomyopathy) the underlying mutation is also present in blood DNA and the disease follows a maternal inheritance. In patients carrying mutations in mtDNA COX subunit genes (COI-III) the histological picture of the muscle biopsy is characteristic, most of the fibers are COX negative, only a few fibers stain positive on COX stain. In a relatively high percent of cases, a prominent lipid accumulation is also present.
The underlying gene defect is heterogenous. The activities of the respiratory chain enzymes may direct the genetic diagnostics:
- Complex IV (COX) deficiency: mtDNA COI-III in muscle DNA
- Complex III deficiency and rhabdomyolysis: mtDNA Cyt
- Combined deficiency: mtDNA tRNA genes, mtDNA deletion/s in muscle-DNA
Prevalence
The occurrence of all mitochondrial disease is 1 : 3000, from this, mitochondrial myopathies are ca. 15%.
Diagnostic
Indication
Method
1. Southern blot / long range PCR for mtDNA deletion(s)
2. Mutation analysis for other mtDNA tRNA, Cyt, COI-III or ND mutations by DNA sequencing (depending on the respiratory enzyme activities in muscle)
Sample Requirement
Muscle DNA (in cases with encephalomyopathy 2 - 4 ml of EDTA-blood)
Duration
1. 1 - 3 weeks
2. 3 - 5 weeks