Diagnosis: Myopathy

Diagnosing coenzyme Q₁₀ deficiency myopathy provides the great benefit of confirming the value of high-dose coenzyme Q₁₀ supplementation. Establishing the diagnosis requires assaying coenzyme Q₁₀ activity in flash-frozen muscle (see Table 3, above). In general, the mitochondrial myopathies are most effectively diagnosed via studies on flash-frozen muscle tissue, which will demonstrate abnormalities on ETC testing.

An Approach to the Diagnosis of Metabolic Myopathies

Aggressively pursuing the diagnostic evaluation of patients with a suspected metabolic myopathy is justified by the potential for therapeutic intervention and a need to provide the patient with prognostic information and appropriate genetic counseling. Proper diagnosis also avoids unnecessary testing and inappropriate therapies such as immunomodulatory therapy for a suspected inflammatory process. A carefully designed evaluation, guided by clinical and laboratory information, will allow proper diagnosis with minimally invasive testing (see Figure 1, p. 14).

For example, the presentation of a patient with recurrent rhabdomyolysis and second-wind phenomenon should prompt blood testing for mutations underlying McArdle’s disease. In contrast, exercise intolerance accompanied by weakness that is exacerbated by carbohydrate intake (out-of-wind phenomenon) suggests GSD type VII (PFK deficiency) that might be confirmed through gene sequencing or muscle-enzyme testing. At times, reaching the diagnosis will require more invasive testing, including histology, histochemistry, and enzyme analysis of muscle tissue, such as in the mitochondrial myopathies (see Table 3, above). Establishing the diagnosis of CPT II deficiency frequently requires enzyme testing of cultured fibroblasts because mutation testing often identifies only a single mutation.

Progressing from careful clinical evaluation to the least invasive testing likely to yield a diagnosis and finally to the muscle biopsy when necessary is a reasonable strategy. Several biochemical genetics laboratories offer “myoglobinuria panels” that can facilitate enzyme testing. If the decision is made to proceed to muscle biopsy, the importance of careful planning to ensure adequate sampling, processing, and preservation cannot be overstated. Collaboration with all of the consultants involved, including the rheumatologist, metabolic specialist, neurologist, surgeon, primary physician, and biochemical laboratory director under the direction of an identified team leader will enhance the chances of establishing a correct diagnosis in a timely, cost-effective manner.

Acknowledgements

We wish to thank our patients and colleagues for their support and understanding while we developed the concepts underlying this paper. We thank Dr. Edward Bossen at Duke University for images and Dr. John Shoffner at Medical Neurogenetics for comments.

Dr. Smith is a medical instructor in the division of pediatric neurology, department of pediatrics at Duke University Medical Center in Durham, N. C. Dr. Koeberl is associate professor of pediatrics and molecular genetics and microbiology at Duke University Medical Center.

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