Presented by

Dr. Rita Horvath

Diagnosing primary mitochondrial diseases is challenging in clinical practice.Although, defective oxidative phosphorylation is the common final pathway, it is unknown why different mtDNA or nuclear mutations result in largely heterogeneous and often tissue specific clinical presentations. Mitochondrial tRNA mutations are frequent causes of mitochondrial disease both in children and adults. However numerous nuclear mutations involved in mitochondrial protein synthesis affecting ubiquitously expressed genes have been reported in association with very tissue specific clinical manifestations suggesting that there are so far unknown factors determining the tissue specificity in mitochondrial translation. Most of these gene defects result in histological abnormalities and multiple respiratory chain defects in the affected organs. The clinical phenotypes are usually early-onset, severe, and often fatal, implying the importance of mitochondrial translation from birth. However, some rare, reversible infantile mitochondrial diseases are caused by very specific defects of mitochondrial translation (m.14674T>C, TRMU). Current approaches for diagnosing mitochondrial disorders involve specialist clinical assessment, biochemical analyses and targeted molecular genetic testing. There is now a strong rationale for undertaking first-line genome-wide sequencing, accelerating the speed of diagnosis and avoiding the need for expensive and invasive investigations.