Mitochondrial disorder diagnosis and management- what the pediatric neurologist wants to know

Abstract

Childhood-onset mitochondrial disorders are rare genetic diseases that often manifest with neurological impairment due to altered mitochondrial structure or function. To date, pathogenic variants in 373 genes across the nuclear and mitochondrial genomes have been linked to mitochondrial disease, but the ensuing genetic and clinical complexity of these disorders poses considerable challenges to their diagnosis and management. Nevertheless, despite the current lack of curative treatment, recent advances in next generation sequencing and -omics technologies have laid the foundation for precision mitochondrial medicine through enhanced diagnostic accuracy and greater insight into pathomechanisms. This holds promise for the development of targeted treatments in this group of patients. Against a backdrop of inherent challenges and recent technological advances in mitochondrial medicine, this review discusses the current diagnostic approach to a child with suspected mitochondrial disease and outlines management considerations of particular relevance to paediatric neurologists. We highlight the importance of mitochondrial expertise centres in providing the laboratory infrastructure needed to supplement uninformative first line genomic testing with focused and/or further unbiased investigations where needed, as well as coordinating an integrated multidisciplinary model of care that is paramount to the management of patients affected by these conditions.

Keywords: Exome sequencing; Leigh syndrome; Multi-omics; Muscle biopsy; Treatment; Vitamin.