Ivana Vodopivec1, Tracey A Cho, Joseph F Rizzo, Matthew P Frosch, Katherine B Sims. 1. *Harvard Medical School †Department of Neurology, Massachusetts General Hospital ‡Massachusetts Eye and Ear Infirmary, Neuro-Ophthalmology Service §Massachusetts General Hospital, Neuropathology Service, Boston, MA.
Abstract
INTRODUCTION: Establishing a diagnosis of mitochondrial disease in adults remains a clinician's challenge. We report a case of syndrome reminiscent of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in an adult patient who carries m.10158T>C mutation in complex I respiratory chain gene MT-ND3 (mitochondrially encoded NADH dehydrogenase 3). CASE REPORT: This 26-year-old man from Thailand presented with new-onset headaches, seizures, stroke-like episodes, and poor vision due to optic neuropathy and cortical blindness. Instead of expected mutations in the mitochondrial tRNA gene that are frequently associated with MELAS, the mutation in MT-ND3 with variable tissue heteroplasmy (blood 5.3%, muscle 89.5%) was demonstrated. The patient's clinical features, blood biomarkers, neuroimaging findings, muscle biopsy with histochemical and functional in vitro analysis, and genetic studies were analyzed and compared with all previously reported ND3 disease cases. CONCLUSIONS: ND3 disease due to m.10158T>C mutation was previously described only in patients with Leigh or Leigh-like syndrome. Our findings thus indicate that ND3 disease can manifest with atypical phenotype in adults. The diagnosis of mitochondrial disease caused by other than typical MELAS-associated mutations in adults with stroke-like episodes, headaches, and seizures should be considered. An analysis of tissue other than blood, which is more likely to harbor a tissue-specific mitochondrial DNA mutation at a measurable level, may be necessary for diagnosis.
INTRODUCTION: Establishing a diagnosis of mitochondrial disease in adults remains a clinician's challenge. We report a case of syndrome reminiscent of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in an adult patient who carries m.10158T>C mutation in complex I respiratory chain gene MT-ND3 (mitochondrially encoded NADH dehydrogenase 3). CASE REPORT: This 26-year-old man from Thailand presented with new-onset headaches, seizures, stroke-like episodes, and poor vision due to optic neuropathy and cortical blindness. Instead of expected mutations in the mitochondrial tRNA gene that are frequently associated with MELAS, the mutation in MT-ND3 with variable tissue heteroplasmy (blood 5.3%, muscle 89.5%) was demonstrated. The patient's clinical features, blood biomarkers, neuroimaging findings, muscle biopsy with histochemical and functional in vitro analysis, and genetic studies were analyzed and compared with all previously reported ND3 disease cases. CONCLUSIONS: ND3 disease due to m.10158T>C mutation was previously described only in patients with Leigh or Leigh-like syndrome. Our findings thus indicate that ND3 disease can manifest with atypical phenotype in adults. The diagnosis of mitochondrial disease caused by other than typical MELAS-associated mutations in adults with stroke-like episodes, headaches, and seizures should be considered. An analysis of tissue other than blood, which is more likely to harbor a tissue-specific mitochondrial DNA mutation at a measurable level, may be necessary for diagnosis.