Manipal Journal of Medical Sciences


Mitochondrial disease refers to a large spectrum of disorders involving defective cellular energy production. Primary mitochondrial disease (PMD) is diagnosed clinically and by genetic testing of mitochondrial and nuclear DNA. However, many disorders have the ‘mitochondrial’ phenotype without an identifiable genetic defect. Even muscle biopsy can be markedly abnormal either due to a PMD or a non-mitochondrial disorder (NMD) affecting mitochondria and giving rise to secondary mitochondrial dysfunction (SMD). Many patients can have clinical signs of mitochondrial dysfunction based on their phenotype, biomarkers, imaging, and muscle biopsy. In these cases, it is often tempting to assign a patient’s phenotype to ‘mitochondrial disease’ but many times it is actually SMD while primary process may be distinct from mitochondria. Fortunately, rapid advances in molecular testing, made possible by next generation sequencing, have been effective in establishing accurate diagnoses to distinguish between PMD and SMD. This is important, since their treatments and prognoses can be quite different. In the absence of the ability to distinguish between PMD and SMD, treating SMD with standard treatments used to treat PMD, can be effective. In this article, the latest research regarding mitochondrial disease/dysfunction is reviewed. In addition, representative examples are illustrated where the distinction between PMD and SMD is crucial for diagnosis and treatment