Background: Mitochondrial disorders are a common cause of inherited genetic disorders with a prevalence of about one in five thousand, with the neurological organ system being most common. Although Chronic progressive external ophthalmoplegia (CPEO) can be commonly seen in patients with mitochondrial disease, extrapyramidal features, including Parkinsonism and dystonia, have also been increasingly recognized as important associated manifestations.
Objective: We report a case of mitochondrial CPEO with late-onset extrapyramidal dysfunction associated with a mitochondrial DNA (mtDNA) variant of uncertain significance.
Result – We present a 47-year-old female with bilateral ptosis, complete external ophthalmoplegia, and mild bulbar weakness as a teenager. Family history was unremarkable. Orbital MRI found paper thin extraocular muscles. Her PABPN1 and POLG were negative. She had negative Acetylcholine Receptor Antibodies and anticardiolipin levels. An EMG/NCS found evidence of a non-inflammatory myopathy. Lab work revealed intermittent elevated lactic acid levels consistent with a mitochondrial disorder. In her fifth decade of life, she developed extrapyramidal dysfunction manifested by mild rigidity in all extremities and a pill-rolling tremor of her left hand. A mitochondrial full genome analysis was performed, which found a mutation at mitochondrial DNA 14693 A>G, which, although reported as a variant of uncertain significance, has been found in mitochondrial disorders such as MELAS.
Conclusion –This case highlights the phenotypic heterogeneity of mitochondrial disorders. The late emergence of extrapyramidal symptoms decades after CPEO onset expands the recognized clinical spectrum of the m.14693A>G variant and emphasizes the need for long-term neurological monitoring in patients with mitochondrial myopathies. In this case, treatment with L-carnitine, CoQ10, L-arginine, and Leucovorin improved her symptoms. We believe this case represents a novel pathogenic mitochondrial disorder.