Diagnosis of Mitochondrial Disorders

Genetic testing is essential for the diagnosis of mitochondrial diseases.

• In case of suspected mitochondrial disease , Next generation sequencing with gene dosage of nuclear DNA (n DNA ) and mitochondrial DNA (mt DNA) from blood or urine sediment  or affected tissues like muscle , buccal swab, liver etc., can be done .
• Mutations, rearrangements, or deletions that are tissue specific are identified  by Tissue-based testing
•  Genetic consultation/ counselling  is also advised.

Biochemical testing in blood, urine, and spinal fluid

• Evaluation of selected mitochondrial biomarkers in blood, urine, and spinal fluid such as the measurements of lactate and pyruvate in plasma and cerebrospinal fluid (CSF), plasma, urine, and CSF amino acids, plasma acyl carnitines, and urine organic acids.
• Lactate elevation occurs because the flux through glycolysis overwhelms the utilization of pyruvate in the mitochondria. Elevated plasma lactate (>3 mmol/l), in a properly collected sample, suggests the presence of mitochondrial dysfunction. This can be due either to primary mitochondrial disease or, secondarily, to organic acidemias, other inborn errors of metabolism, toxins, tissue ischemia, and certain other diseases.
• In patients with associated neurologic symptoms, elevated CSF lactate can be a helpful marker of mitochondrial disease .
• Quantitative amino acid analysis like  alanine, glycine, proline, and threonine in blood or spinal fluid is commonly obtained when evaluating a patient with possible mitochondrial disease. This occurs due to the altered redox state created by respiratory chain dysfunction including alanine, glycine, proline, and threonine

Neuroimaging

• Structural alterations in neuroimaging like computed tomography and magnetic resonance imaging of the brain have been used in the diagnosis of mitochondrial disorders, depending on the type of mitochondrial disorder and type of central nervous system involvement.