Blood and urine studies are often the first step in diagnosing mitochondrial disease. These studies typically include measurements of lactate and pyruvate in plasma, cerebrospinal fluid (CSF), and urine, as well as measuring specific amino and organic acids. Additional tests may be added, including neuroimaging, electromyography (EMG) to measure muscle activity, and nerve conduction studies (NCS). Some of the “Red Flag” symptoms in the brain, such as stroke-like lesions are classic findings in mitochondrial disease, but cannot be used solely for disease confirmation.
Primary mitochondrial diseases (PMD) result from mutations in the nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Genetic studies of these two sources of DNA have replaced muscle biopsies as the gold standard for diagnosis. Unfortunately, genetic testing is expensive and requires a good deal of evidence that the cause of symptoms is mitochondrial before insurance will cover this level of testing. Some health insurance plans currently do not cover genetic testing for PMD, and patients must rely on other methods of diagnosis. When mitochondrial disease is strongly suspected but genetic studies do not reveal a known mitochondrial disease-causing mutation, patients may still receive a clinical diagnosis of mitochondrial disease.
Clinicians are using muscle and tissue biopsies less frequently for mitochondrial diagnosis because these tests may not be as comprehensive as genetic testing and may not be well tolerated by mitochondrial disease patients. PMD and mitochondrial dysfunction (secondary) cannot be differentiated with laboratory tissue testing alone. Functional tests – evaluations of how mitochondria are functioning in cells – remain important measures of mitochondrial function. In patients with a disease of muscle tissue, certain other neuromuscular diseases can be excluded by a muscle biopsy.