Mitochondrial disease is difficult to diagnosis because of the wide range of potential manifestations, and the lack of a definitive test. The diagnosis is usually made by a physician who specializes in mitochondrial medicine, who is often a clinical geneticist or a neurologist.
The diagnosis is generally first suspected based on the presence of a combination of signs and symptoms involving different body systems that are otherwise difficult to explain. Usually, if there are symptoms in three or more different systems, or a young patient is given three or more “diagnoses,” further investigation of mitochondrial disease is warranted. Symptoms that come and go, especially if they are functional or dysautonomic in nature, deserve additional consideration for the possibility of a mitochondrial cause.
The diagnostic process generally includes obtaining a thorough medical history, a detailed family medical history, a physical examination, and variable laboratory testing. The laboratory testing performed varies depending on the individual case, but may include metabolic testing in body fluids (especially blood and urine), DNA testing, tissue biopsy (e.g. muscle or skin), and/or imaging (e.g. brain MRI). Some testing during illness, or at other times of physiological stress, may be requested. Testing for non-mitochondrial disorders that can look like mitochondrial disease is often an important part of the diagnostic work-up.