title: MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options.
abstract: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS syndrome without proven efficacy.
authors.affiliation: Division of Clinical Genetics and Metabolic Disorders, Department of Pediatrics, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: Ayman W
authors.initials: AW
authors.lastname: El-Hattab
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.affiliation: Singleton Department of Radiology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jones
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: fscaglia@bcm.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000628:therapy; D002331:Carnitine / Q000627:therapeutic use; D004700:Endocrine System Diseases / Q000378:metabolism / Q000628:therapy; D004735:Energy Transfer; D005767:Gastrointestinal Diseases / Q000378:metabolism / Q000628:therapy; D006801:Humans; D017241:MELAS Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000378:metabolism / Q000628:therapy; D009422:Nervous System Diseases / Q000378:metabolism / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D012356:RNA, Transfer, Leu / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D012356:RNA, Transfer, Leu; D014451:Ubiquinone; D009569:Nitric Oxide; D001120:Arginine; C024989:coenzyme Q10; D002331:Carnitine
keywords: Angiopathy; Arginine; Citrulline; Encephalomyopathy; Endothelial dysfunction; Lactic acidosis; Mitochondrial diseases; Nitric oxide deficiency