melas syndrome

Summary

Summary: A mitochondrial disorder characterized by focal or generalized seizures, episodes of transient or persistent neurologic dysfunction resembling strokes, and ragged-red fibers on muscle biopsy. Affected individuals tend to be normal at birth through early childhood, then experience growth failure, episodic vomiting, and recurrent cerebral insults resulting in visual loss and hemiparesis. The cortical lesions tend to occur in the parietal and occipital lobes and are not associated with vascular occlusion. VASCULAR HEADACHE is frequently associated and the disorder tends to be familial. (From Joynt, Clinical Neurology, 1992, Ch56, p117)

Top Publications

  1. Sproule D, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008;1142:133-58 pubmed publisher
    ..Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities...
  2. Connolly B, Feigenbaum A, Robinson B, Dipchand A, Simon D, Tarnopolsky M. MELAS syndrome, cardiomyopathy, rhabdomyolysis, and autism associated with the A3260G mitochondrial DNA mutation. Biochem Biophys Res Commun. 2010;402:443-7 pubmed publisher
    ..kindred reported the phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) in association with the A3260G mtDNA mutation...
  3. Katayama Y, Maeda K, Iizuka T, Hayashi M, Hashizume Y, Sanada M, et al. Accumulation of oxidative stress around the stroke-like lesions of MELAS patients. Mitochondrion. 2009;9:306-13 pubmed publisher
    ..Increased oxidative stress and insufficient defense could be involved in the pathogenesis of the spreading lesions in MELAS...
  4. Kolb S, Costello F, Lee A, White M, Wong S, Schwartz E, et al. Distinguishing ischemic stroke from the stroke-like lesions of MELAS using apparent diffusion coefficient mapping. J Neurol Sci. 2003;216:11-5 pubmed
    ..We conclude that conventional MRI when used with diffusion-weighted MR imaging may be invaluable in detecting mitochondrial-related CNS dysfunction...
  5. Wang X, Noguchi K, Takashima S, Hayashi N, Ogawa S, Seto H. Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema. Neuroradiology. 2003;45:640-3 pubmed
    ..In the chronic stage, the ADC became higher than that in normal brain. We therefore suggest that the stroke-like episodes did not cause vasogenic oedema but were related to energy failure and cytotoxic oedema...
  6. Sheerin F, Pretorius P, Briley D, Meagher T. Differential diagnosis of restricted diffusion confined to the cerebral cortex. Clin Radiol. 2008;63:1245-53 pubmed publisher
    ..DWI also contributes useful diagnostic information in a range of other conditions. In this review we describe the magnetic resonance imaging (MRI) features of a number of conditions characterized by cortical diffusion restriction (CDR)...
  7. Jian Ren L. Precipitation of stroke-like event by chickenpox in a child with MELAS syndrome. Neurol India. 2005;53:323-5 pubmed
  8. Qi Y, Zhang Y, Wang Z, Yang Y, Yuan Y, Niu S, et al. Screening of common mitochondrial mutations in Chinese patients with mitochondrial encephalomyopathies. Mitochondrion. 2007;7:147-50 pubmed
    ..For A3243G mutation, the proportion of mutant mtDNA was not related to severity of the disease but to the age of onset...
  9. Pronicki M, Sykut Cegielska J, Mierzewska H, Tonska K, Karczmarewicz E, Iwanicka K, et al. Diversity of clinical symptoms in A3243G mitochondrial DNA mutation (MELAS syndrome mutation). Med Sci Monit. 2002;8:CR767-73 pubmed
    ..MELAS (mitochondrial myopathy, lactic acidosis and stroke-like episodes) is one of the most common mitochondrial encephalomyopathies...

More Information

Publications62

  1. Suzuki T, Nagao A, Suzuki T. Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases. Annu Rev Genet. 2011;45:299-329 pubmed publisher
    ..These nuclear factors are also targets of pathogenic mutations linked to various diseases, indicating the functional importance of mt tRNAs for mitochondrial activity...
  2. Scaglia F, Northrop J. The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options. CNS Drugs. 2006;20:443-64 pubmed
    ..As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years...
  3. Kaufman K, Zuber N, Rueda Lara M, Tobia A. MELAS with recurrent complex partial seizures, nonconvulsive status epilepticus, psychosis, and behavioral disturbances: case analysis with literature review. Epilepsy Behav. 2010;18:494-7 pubmed publisher
    ..Further education of medical professionals regarding this disorder, its appropriate management, and the significance of NCSE is indicated to avoid delay of treatment...
  4. Iizuka T, Sakai F, Kan S, Suzuki N. Slowly progressive spread of the stroke-like lesions in MELAS. Neurology. 2003;61:1238-44 pubmed
    ..Little is known about temporal and spatial progression of the stroke-like lesion during the acute stage of the stroke-like episode in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)...
  5. Abe K, Yoshimura H, Tanaka H, Fujita N, Hikita T, Sakoda S. Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology. 2004;46:113-7 pubmed
    ..Our findings suggest a possible predictive ability of (1)H-MRS, in showing early MELAS lesions and supports the hypothesis that mitochondrial metabolic dysfunction may precedes abnormalities on DWI...
  6. Glatz C, D Aco K, Smith S, Sondheimer N. Mutation in the mitochondrial tRNA(Val) causes mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. Mitochondrion. 2011;11:615-9 pubmed publisher
    ..The m.1630A>G mutation impairs oxygen consumption, affects the stability of the MTTV and reduces the levels of subunits of the electron transport chain...
  7. Santa K. Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Pharmacotherapy. 2010;30:1179-96 pubmed publisher
    ..Caused most frequently by an A-to-G point mutation at the 3243 position in the mitochondrial DNA, MELAS syndrome has a broad range of clinical manifestations and a highly variable course...
  8. Ravn K, Wibrand F, Hansen F, Horn N, Rosenberg T, Schwartz M. An mtDNA mutation, 14453G-->A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome. Eur J Hum Genet. 2001;9:805-9 pubmed
    ..ND6 subunit of the NADH:ubiquinone oxidoreductase (complex I of the respiratory chain) in a patient with MELAS syndrome. The mutation causes a change from alanine to valine in the most conserved region of the ND6 subunit...
  9. Bhati R, Sheridan B, Mill M, Selzman C. Heart transplantation for progressive cardiomyopathy as a manifestation of MELAS syndrome. J Heart Lung Transplant. 2005;24:2286-9 pubmed
  10. Sangkhathat S, Kusafuka T, Yoneda A, Kuroda S, Tanaka Y, Tanaka M, et al. Renal cell carcinoma in a pediatric patient with an inherited mitochondrial mutation. Pediatr Surg Int. 2005;21:745-8 pubmed
    ..With this information, we speculated a role of mitochondria mutation in the pathogenesis of this cancer...
  11. Wang Z, Xiao J, Xie S, Zhao D, Liu X, Zhang J, et al. MR evaluation of cerebral oxygen metabolism and blood flow in stroke-like episodes of MELAS. J Neurol Sci. 2012;323:173-7 pubmed publisher
    ..The increased utilization of oxygen in an acute lesion is a novel finding in our study, which might play a role in the oxidative stress...
  12. Karkos P, Waldron M, Johnson I. The MELAS syndrome. Review of the literature: the role of the otologist. Clin Otolaryngol Allied Sci. 2004;29:1-4 pubmed
    ..A high index of suspicion is required because this hearing loss is part of a syndrome for which early diagnosis and intervention is required...
  13. Feddersen B, Bender A, Arnold S, Klopstock T, Noachtar S. Aggressive confusional state as a clinical manifestation of status epilepticus in MELAS. Neurology. 2003;61:1149-50 pubmed
  14. Abu Amero K, Zou M, Shi Y. Mitochondrial A135149 mutation without MELAS but in association with papillary thyroid carcinoma. Clin Genet. 2004;66:569-70 pubmed
  15. Kärppä M, Syrjälä P, Tolonen U, Majamaa K. Peripheral neuropathy in patients with the 3243A>G mutation in mitochondrial DNA. J Neurol. 2003;250:216-21 pubmed
    ..Higher age and male gender were associated with an increased risk of neuropathy. Our results show that peripheral neuropathy is not uncommon in patients with the 3243A > G mutation, and they also may have an increased risk of CTS...
  16. Shanske S, Pancrudo J, Kaufmann P, Engelstad K, Jhung S, Lu J, et al. Varying loads of the mitochondrial DNA A3243G mutation in different tissues: implications for diagnosis. Am J Med Genet A. 2004;130A:134-7 pubmed
    ..We conclude that urinary sediment and cheek mucosa are tissues of choice for the diagnosis of mtDNA mutations, as they are easy to obtain and the mutation load is almost always greater than in blood...
  17. Kim J, Lim M, Jeon T, Rha J, Rha J, Eo H, et al. Diffusion and perfusion characteristics of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) in thirteen patients. Korean J Radiol. 2011;12:15-24 pubmed publisher
  18. Aouad M, Gerges F, Baraka A. Resistance to cisatracurium in a patient with MELAS syndrome. Paediatr Anaesth. 2005;15:1124-7 pubmed
    ..We present a patient with MELAS syndrome who underwent Nissen fundoplication and gastrojejunostomy...
  19. Bi W, Baehring J, Lesser R. Evolution of brain imaging abnormalities in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. J Neuroophthalmol. 2006;26:251-6 pubmed
    ..The patient's visual function improved, but severe atrophy of gray and white matter was visible on MRI...
  20. Sasarman F, Antonicka H, Shoubridge E. The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2. Hum Mol Genet. 2008;17:3697-707 pubmed publisher
  21. Liolitsa D, Rahman S, Benton S, Carr L, Hanna M. Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?. Ann Neurol. 2003;53:128-32 pubmed
    ..Histochemistry was normal. Our observations add to the evidence that mitochondrial ND5 protein coding gene mutations frequently associate with the MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS...
  22. Iizuka T, Sakai F, Ide T, Miyakawa S, Sato M, Yoshii S. Regional cerebral blood flow and cerebrovascular reactivity during chronic stage of stroke-like episodes in MELAS -- implication of neurovascular cellular mechanism. J Neurol Sci. 2007;257:126-38 pubmed
    ..Ischemic vascular hypothesis as a causative role in the pathogenesis of stroke-like episodes in MELAS remains to be debated...
  23. Bernier F, Boneh A, Dennett X, Chow C, Cleary M, Thorburn D. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology. 2002;59:1406-11 pubmed
    ..Respiratory chain (RC) disorders are clinically, biochemically, and molecularly heterogeneous. The lack of standardized diagnostic criteria poses difficulties in evaluating diagnostic methodologies...
  24. Choi B, Hwang J, Kim J, Cho E, Cho S, Hwang S, et al. A MELAS syndrome family harboring two mutations in mitochondrial genome. Exp Mol Med. 2008;40:354-60 pubmed
    ..This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders...
  25. Manwaring N, Jones M, Wang J, Rochtchina E, Howard C, Mitchell P, et al. Population prevalence of the MELAS A3243G mutation. Mitochondrion. 2007;7:230-3 pubmed
    ..24%; 95% CI 0.10-0.49%); much higher than previously reported. All had mild to moderate hearing loss. Our findings indicate that subjects with the 3243A>G mtDNA mutation could be markedly under-recognised in the community...
  26. El Hattab A, Hsu J, Emrick L, Wong L, Craigen W, Jahoor F, et al. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation. Mol Genet Metab. 2012;105:607-14 pubmed publisher
    ..This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline...
  27. Marotta R, Reardon K, McKelvie P, Chiotis M, Chin J, Cook M, et al. Association of the MELAS m.3243A>G mutation with myositis and the superiority of urine over muscle, blood and hair for mutation detection. J Clin Neurosci. 2009;16:1223-5 pubmed publisher
    ..This report highlights the need to screen various tissues to achieve an accurate mitochondrial genetic diagnosis and suggests the likelihood of myositis arising secondary to the MELAS MT-TL1 m.3243A>G mutation...
  28. Davidson M, Walker W, Hernandez Rosa E. The m.3243A>G mtDNA mutation is pathogenic in an in vitro model of the human blood brain barrier. Mitochondrion. 2009;9:463-70 pubmed publisher
    ..These data support our hypothesis that respiratory chain defects in the components of the BBB cause changes in permeability...
  29. Mima A, Shiota F, Matsubara T, Iehara N, Akagi T, Abe H, et al. An autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with intestinal bleeding in chronic renal failure. Ren Fail. 2011;33:622-5 pubmed publisher
    ..Multiple organ failure due to the mutation of mitochondrial DNA with gastrointestinal bleeding is not a common...
  30. Zhang Z, Niu S, Liang X, Jian F, Wang Y. Vascular involvement in the pathogenesis of mitochondrial encephalomyopathies. Neurol Res. 2010;32:403-8 pubmed publisher
    ..Furthermore, the pathology of muscle vessel was evaluated, to explore the role of vasculopathy and ischemic events in the pathogenesis of mitochondrial encephalomyopathies...
  31. Ito H, Mori K, Harada M, Minato M, Naito E, Takeuchi M, et al. Serial brain imaging analysis of stroke-like episodes in MELAS. Brain Dev. 2008;30:483-8 pubmed publisher
    ..These results suggest that the stroke-like episodes is related to vasogenic edema, hyperperfusion, and neuronal damage. Acute oxidative phosphorylation defect may have a crucial role in the pathophysiology of stroke-like episodes...
  32. Uusimaa J, Moilanen J, Vainionpaa L, Tapanainen P, Lindholm P, Nuutinen M, et al. Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children. Ann Neurol. 2007;62:278-87 pubmed
    ..We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland...
  33. Kubota H, Tanabe Y, Takanashi J, Kohno Y. Episodic hyponatremia in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS). J Child Neurol. 2005;20:116-20 pubmed
    ..Because severe hyponatremia can cause serious complications, clinicians should pay attention to serum sodium levels and maintain them properly in patients with MELAS...
  34. Chou Y, Ou C, Hsu T, Liou C, Lee C, Tso D, et al. Prenatal diagnosis of a fetus harboring an intermediate load of the A3243G mtDNA mutation in a maternal carrier diagnosed with MELAS syndrome. Prenat Diagn. 2004;24:367-70 pubmed
    We prenatally diagnosed MELAS syndrome in a fetus whose mother and older brother had the MELAS-specific A3243G mutation...
  35. Lev D, Nissenkorn A, Leshinsky Silver E, Sadeh M, Zeharia A, Garty B, et al. Clinical presentations of mitochondrial cardiomyopathies. Pediatr Cardiol. 2004;25:443-50 pubmed
    ..Seven patients exhibited a deficiency of a respiratory chain enzyme in the muscle. The MELAS mtDNA point mutation (3243) was found in one patient. Blood lactic acid levels were increased in 5. Brain MRI abnormalities were observed in 4...
  36. Kirino Y, Yasukawa T, Ohta S, Akira S, Ishihara K, Watanabe K, et al. Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease. Proc Natl Acad Sci U S A. 2004;101:15070-5 pubmed
    ..We thus concluded that the UUG codon-specific translational defect of the mutant mt tRNAs(Leu(UUR)) is the primary cause of MELAS at the molecular level. This result could explain the complex I deficiency observed clinically in MELAS...
  37. Karicheva O, Kolesnikova O, Schirtz T, Vysokikh M, Mager Heckel A, Lombes A, et al. Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria. Nucleic Acids Res. 2011;39:8173-86 pubmed publisher
    ..The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes)...
  38. Kaufmann P, Pascual J, Anziska Y, Gooch C, Engelstad K, Jhung S, et al. Nerve conduction abnormalities in patients with MELAS and the A3243G mutation. Arch Neurol. 2006;63:746-8 pubmed
    ..Neuropathy has been associated with several mitochondrial diseases, including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes)...
  39. Feuermann M, Francisci S, Rinaldi T, De Luca C, Rohou H, Frontali L, et al. The yeast counterparts of human 'MELAS' mutations cause mitochondrial dysfunction that can be rescued by overexpression of the mitochondrial translation factor EF-Tu. EMBO Rep. 2003;4:53-8 pubmed
  40. Li R, Guan M. Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes. Mol Cell Biol. 2010;30:2147-54 pubmed publisher
    ..These findings provide new insights into the molecular mechanism of maternally inherited diseases and a step toward therapeutic interventions for these disorders...
  41. Becker R, Laube H, Linn T, Damian M. Insulin resistance in patients with the mitochondrial tRNA(Leu(UUR)) gene mutation at position 3243. Exp Clin Endocrinol Diabetes. 2002;110:291-7 pubmed
    ..The aim of the present investigation was to study the insulin sensitivity index (SI), insulin secretion (AIR(Glucose)) and glucose effectiveness (Sg) in patients with the 3243-mutation...
  42. Thomas J, Lee N, Thompson P. Statins provoking MELAS syndrome. A case report. Eur Neurol. 2007;57:232-5 pubmed
    ..Idiopathic or primary CoQ10 deficiencies have been known to cause mitochondrial encephalomyopathy...
  43. Deschauer M, Tennant S, Rokicka A, He L, Kraya T, Turnbull D, et al. MELAS associated with mutations in the POLG1 gene. Neurology. 2007;68:1741-2 pubmed
  44. Tsujikawa T, Yoneda M, Shimizu Y, Uematsu H, Toyooka M, Ikawa M, et al. Pathophysiologic evaluation of MELAS strokes by serially quantified MRS and CASL perfusion images. Brain Dev. 2010;32:143-9 pubmed publisher
  45. Tzoulis C, Bindoff L. Serial diffusion imaging in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Stroke. 2009;40:e15-7 pubmed publisher
    ..There are, however, 3 recent reports of restricted diffusion in the acute phase of the stroke-like lesions. The purpose of our study was to investigate this apparent paradox...
  46. Alemdar M, Iseri P, Selekler M, Budak F, Demirci A, Komsuoglu S. MELAS presented with status epilepticus and Anton-Babinski syndrome; value of ADC mapping in MELAS. J Neuropsychiatry Clin Neurosci. 2007;19:482-3 pubmed
  47. Tzoulis C, Bindoff L. Melas associated with mutations in the polg1 gene. Neurology. 2008;70:1054; author reply 1054-5 pubmed publisher
  48. Iizuka T, Sakai F, Suzuki N, Hata T, Tsukahara S, Fukuda M, et al. Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome. Neurology. 2002;59:816-24 pubmed
    ..The pathogenesis of stroke-like episodes in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) remains unknown...
  49. Park H, Davidson E, King M. The pathogenic A3243G mutation in human mitochondrial tRNALeu(UUR) decreases the efficiency of aminoacylation. Biochemistry. 2003;42:958-64 pubmed
    ..These results also suggest that the A3243G and T3271C mutations may have distinct mechanisms of pathogenesis...
  50. Ohno A, Mori A, Doi R, Yonenaga Y, Asano N, Uemoto S. Successful left hemihepatectomy and perioperative management of a patient with biliary cystadenocarcinoma, complicated with MELAS syndrome: report of a case. Surg Today. 2010;40:878-82 pubmed publisher
    ..The patient in this report has remained free of liver dysfunctions and cancer recurrence for 2 years following the hepatectomy. This is the first report of a successful major hepatectomy for a patient with MELAS...
  51. Bouchet C, Steffann J, Corcos J, Monnot S, Paquis V, Rotig A, et al. Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development. J Med Genet. 2006;43:788-92 pubmed
    ..Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome...
  52. Lau K, Yang S, Haddad M, Butani L, Makker S. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes syndrome with hypothyroidism and focal segmental glomerulosclerosis in a paediatric patient. Int Urol Nephrol. 2007;39:941-6 pubmed
    ..The purpose of this report is to increase the awareness of health-care professionals, especially in the fields of paediatrics, neurology, endocrinology and nephrology, regarding the manifestations and complications of MELAS...
  53. Chou H, Liang W, Zhang Q, Goto Y, Jong Y. Clinical and genetic features in a MELAS child with a 3271T>C mutation. Pediatr Neurol. 2008;38:143-6 pubmed publisher
    ..The results suggest that urinary sediments may be an alternative tissue of choice which can be obtained noninvasively in the diagnosis of mitochondrial DNA 3271T>C mutations...