To describe the phenotypic spectrum and long-term outcomes of mitochondrial myopathies (MtM) diagnosed in adulthood.

MtMs are frequently recognized in childhood as part of a broader multisystem disorder and often overlooked in adults.

Retrospective review of clinical and laboratory features of adult patients diagnosed with MtM at Mayo Clinic (2005-2021).

We identified 94 patients (81 genetically-defined and 13 histopathologically-defined); 48 females. Median age at diagnosis was 48 years (range: 18-80). Diagnosis was often delayed (median 11 years, range: 1-59). Syndromic presentations included chronic progressive external ophthalmoplegia (CPEO)/CPEO+ (37 patients); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (13); Kearns-Sayre syndrome (2); sensory ataxic neuropathy, dysarthria, ophthalmoplegia (2); myoclonic epilepsy with ragged-red fibers (1); mitochondrial neurogastrointestinal encephalomyopathy (1); and MtM with lactic acidosis and sideroblastic anemia (1). Non-syndromic presentations included a multisystem disorder (23) and isolated myopathy (14). Initial symptoms were commonly ocular (35) or hearing loss (18). Frequently reported symptoms at presentation included proximal weakness (76), generalized fatigue (62), sensorineural hearing loss (42), dysphagia (28), migraine (27), and/or exercise intolerance (22). 53 patients had accompanying peripheral neuropathy. Other involved systems included gastrointestinal (31), endocrine (21), psychiatric (21), cardiac (18), and pulmonary (18). Resting creatine kinase and lactate levels were infrequently elevated (35% and 45%, respectively). All tested patients (6) had elevated GDF15 level (range: 1369-6000). Electroneuromyography demonstrated proximal (33), diffuse (20), and/or cranial (15) myopathy, or was normal (9). Fibrillation potentials (20) and myotonic discharges (4) were infrequent. Pathogenic variants were more common in mitochondrial than nuclear DNA (52 versus 29 patients). M.3243A>G (22) and mutations in POLG1 (18) were most common. Clinical-histopathological-molecular correlation and long-term outcomes will be presented at the Meeting.

MtMs diagnosed in adulthood have a wide phenotypic spectrum, most commonly presenting as CPEO/CPEO+ or a multisystem disorder, with significant associated morbidity.