To describe a rare case of Kearns- Sayre Syndrome (KSS) with the MELAS phenotype.

KSS and MELAS are mitochondrial disorders due to mutations in mitochondrial DNA. KSS is characterized by progressive external ophthalmoplegia (PEO), pigmentary retinopathy, and cardiomyopathy while MELAS is associated with stroke like episodes, lactic acidosis and encephalopathy.

We present a 68-year-old man with gradually progressive bilateral sensorimotor weakness and ophthalmoplegia since the age of 20s. Patient was originally diagnosed with multiple sclerosis at the age of 32 years. Over the years, patient developed limb paresthesias, gait instability, diplopia, dysphagia and slurred speech. Laboratory testing was significant for elevated blood lactic acid on repeated testing.  MRI brain showed old lacunar infarct and lesions consistent with mitochondrial disease. MRI spinal cord was unremarkable. Family history was significant for ptosis and diplopia in his sisters, suggestive of dominant inheritance pattern most likely mitochondrial disorders.

EMG/NCS showed non-irritable myopathy without evidence of neuropathy. Genetic testing for oculopharyngeal muscular dystrophy was negative. Muscle biopsy did not reveal findings suggestive of mitochondrial myopathy. There was no evidence of vasculitis, inflammation or inclusion bodies. The cryostat fresh frozen tissue stained with H&E, modified Gomori trichrome and PAS confirmed intact fascicular architecture. There was no evidence of ragged red fibers or abnormal staining pattern on oxidative or dehydrogenase staining. Nonspecific esterase highlighted a few angular atrophic fibers, but no fibers with active myophagocytosis or degeneration. Further genetic testing showed a 6kb duplication-rearrangement in the mitochondrial DNA in approximately 5% of the mitochondrial genome. No deletions were noted. Even though this duplication is suggestive of KSS, the clinical phenotype correlates with MELAS.

Patient died of cardiological complications at the age of 70 years. Although the patient has a MELAS phenotype, genetic testing was consistent with KSS. This case highlights the significant overlap between mitochondrial DNA disorders.