The A8344G mutation in mitochondrial DNA associated with stroke-like episodes and gastrointestinal dysfunction

• DOI: 10.1007/s00401-002-0604-y
• Publication Date: 2019-12-12T02:19:19Z
• Authors: Kurenai Tanji; Josep Gamez; Carles Cervera; Fermin Mearin; Arantxa Ortega; Javier de la Torre; Julio Montoya; Antoni L. Andreu; Salvatore DiMauro; Eduardo Bonilla
• Keywords: Adult; 0301 basic medicine; Gastrointestinal Diseases; Histocytochemistry; Brain; Cytochrome-c Oxidase Deficiency; DNA, Mitochondrial; Immunohistochemistry; MERRF Syndrome; 3. Good health; Electron Transport Complex IV; Stroke; 03 medical and health sciences; Intestine, Small; Mutation; Humans; RNA, Transfer, Lys; Female

We report an unusual case of encephalo-entero-myopathy associated with the A8344G mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). This patient had mitochondrial myopathy, multiple lipomatosis, mild hearing loss, stroke-like episodes, and paralytic ileus, but she lacked the canonical clinical features of MERRF, myoclonus, epilepsy, or ataxia. We conducted genetic, biochemical, histochemical, and immunohistochemical studies in skeletal muscle, brain, intestine, and lipoma tissue. The mutation was abundant in all tissues, and cytochrome c oxidase (COX) activity was selectively decreased in brain and small intestine. COX deficiency was also documented histochemically and immunohistochemically in the small intestine, suggesting that mitochondrial dysfunction played a role in the pathogenesis of paralytic ileus. This case illustrates an unusual and dramatic clinical phenotype of the A8344G mutation, characterized by stroke-like episodes and acute ileus.