Updates on Mitochondrial Myopathies

Abstract

Purpose of review: Mitochondrial myopathies (MM) are a genetically and clinically heterogeneous group of disorders that remain underrecognized in adult and pediatric neurology. This review aims to provide a clinically useful tool for guiding diagnosis and management of MM. We also highlight the rapidly evolving diagnostic and therapeutic landscape, including novel diagnostic approaches and disease-modifying interventions.

Recent findings: Large cohort data highlight key clinical subtypes - fixed myopathies, syndromic forms, and metabolic myopathies- with distinct diagnostic implications. Novel tools such as GDF-15, long-read mtDNA sequencing, and multi-omic approaches are enhancing diagnostic sensitivity. Emerging therapies for TK2 deficiency and precision mitochondrial gene editing are progressing rapidly, with several nearing regulatory decisions. Numerous preclinical therapeutic strategies are currently under development, offering promise for improving outcomes in these otherwise devastating disorders. Recognizing MM in clinical settings is essential for timely diagnosis, to guide prognosis and family planning as well as provide access to emerging treatment. A tiered diagnostic approach and integration of new genomic technologies can improve outcomes.

Human and animal rights: This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Exercise intolerance; Mitochondrial myopathy; Muscle biopsy; Next-generation sequencing; Rhabdomyolysis; TK2 deficiency.