Delay in diagnosing a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome who presented with status epilepticus and lactic acidosis: a case report

Ahmad F Alenezi 1 2 3, Mariam A Almelahi 4, Feten Fekih-Romdhana 5 6, Haitham A Jahrami 7 8

Affiliations

10 October 2022

-

doi: 10.1186/s13256-022-03613-2

Abstract

Background: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome is a rare mitochondrial genetic disorder that can present with a variety of clinical manifestations, including stroke, hearing loss, seizures, and lactic acidosis. The most common genetic mutation associated with this syndrome is M.3243A>G. The main underlying mechanism of the disease relates to protein synthesis, energy depletion, and nitric oxide deficiency. Controlling disease complications and improving patient quality of life are the primary aims of treatment options.

Case presentation: A 28-year-old Arabic female visited Al-Amiri Hospital in Kuwait. The patient was newly diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome following her admission as a case of status epilepticus requiring further investigation. The patient's seizures were controlled, and she was evaluated to rule out the most serious complications by carrying out appropriate clinical, laboratory, and radiological imaging. The patient was discharged from the hospital after 2 weeks with a follow-up plan.

Conclusion: This case report emphasizes the importance of considering mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome as a potential cause of status epilepticus with lactic acidosis in a young female patient with a past history of stroke-like episodes. It also stresses the most important workup to rule out every possible life-threatening complication to improve patients' lives.

Keywords: Lactic acidosis; MELAS syndrome; Mitochondrial encephalopathies; Status epilepticus; Stroke-like episode.

Conflict of interest statement

The authors declare that there are no conflicts of interest in this study.

Figures

Fig. 1 Brain MRI: (A) left temporal, parietal cortical and subcortical patchy areas of high signal intensity on T2 and Fluid attenuated inversion recovery Wigs (FLAIR WIGs). (B) left occipital and temporal patchy areas of high signal intensity

Fig. 1 Brain MRI: (A) left temporal, parietal cortical and subcortical patchy areas of high signal intensity on T2 and Fluid attenuated inversion recovery Wigs (FLAIR WIGs). (B) left occipital and temporal patchy areas of high signal intensity

Similar articles

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome in pregnancy.

Balachandran Nair D, Bloomfield M, Parasuraman R, Howe DT.BMJ Case Rep. 2021 Apr 7;14(4):e235111. doi: 10.1136/bcr-2020-235111.PMID: 33827862 Free PMC article.

Wernicke Encephalopathy Mimicking MELAS.

Finsterer J.Medicina (Kaunas). 2022 May 13;58(5):660. doi: 10.3390/medicina58050660.PMID: 35630076 Free PMC article.

Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation.

Scarcella S, Dell'Arti L, Gagliardi D, Magri F, Govoni A, Velardo D, Mainetti C, Minorini V, Ronchi D, Piga D, Comi GP, Corti S, Meneri M.BMC Neurol. 2023 Apr 24;23(1):165. doi: 10.1186/s12883-023-03198-3.PMID: 37095452 Free PMC article.

[MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes].

Murakami H, Ono K.Brain Nerve. 2017 Feb;69(2):111-117. doi: 10.11477/mf.1416200650.PMID: 28202819 Review. Japanese.

MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options.

El-Hattab AW, Adesina AM, Jones J, Scaglia F.Mol Genet Metab. 2015 Sep-Oct;116(1-2):4-12. doi: 10.1016/j.ymgme.2015.06.004. Epub 2015 Jun 15.PMID: 26095523 Review.

KMEL References

https://pubmed.ncbi.nlm.nih.gov/

References

  1.  
    1. El-Hattab AW, Adesina AM, Jones J, Scaglia F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab. 2015;116(1–2):4–12. doi: 10.1016/j.ymgme.2015.06.004. - DOI - PubMed
  2.  
    1. Sproule DM, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes. Ann N Y Acad Sci. 2008;1142(1):133–158. doi: 10.1196/annals.1444.011. - DOI - PubMed
  3.  
    1. Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol. 1984;16(4):481–488. doi: 10.1002/ana.410160409. - DOI - PubMed
  4.  
    1. Yatsuga S, Povalko N, Nishioka J, Katayama K, Kakimoto N, Matsuishi T, et al. MELAS: a nationwide prospective cohort study of 96 patients in Japan. Biochim Biophys Acta BBA Gen Subj. 2012;1820(5):619–624. doi: 10.1016/j.bbagen.2011.03.015. - DOI - PubMed
  5.  
    1. Majamaa K, Moilanen JS, Uimonen S, Remes AM, Salmela PI, Kärppä M, et al. Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes: prevalence of the mutation in an adult population. Am J Hum Genet. 1998;63(2):447–454. doi: 10.1086/301959. - DOI - PMC - PubMed
  6.  
    1. Xu M, Kopajtich R, Elstner M, Wang Z, Liu Z, Wang J, et al. Identification of a novel variant in MT-CO3 causing MELAS. Front Genet. 2021;12(12):638749. doi: 10.3389/fgene.2021.638749. - DOI - PMC - PubMed
  7.  
    1. Ghosh R, Dubey S, Bhuin S, Lahiri D, Ray BK, Finsterer J. MELAS with multiple stroke-like episodes due to the variant m.13513G>A in MT-ND5. Clin Case Rep. 2022 doi: 10.1002/ccr3.5361. - DOI - PMC - PubMed
  8.  
    1. Shu J, Zhi X, Chen J, Lei M, Zheng J, Sheng W, et al. Case report: a case of β-ureidopropionase deficiency complicated with MELAS syndrome caused by UPB1 variant and mitochondrial gene variant. Front Pediatr. 2022;21(10):838341. doi: 10.3389/fped.2022.838341. - DOI - PMC - PubMed
  9.  
    1. Goto Y, Nonaka I, Horai S. A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348(6302):651–653. doi: 10.1038/348651a0. - DOI - PubMed
  10.  
    1. Kobayashi Y, Momoi MY, Tominaga K, Momoi T, Nihei K, Yanagisawa M, et al. A point mutation in the mitochondrial tRNALeu (UUR) gene in melas (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) Biochem Biophys Res Commun. 1990;173(3):816–822. doi: 10.1016/S0006-291X(05)80860-5. - DOI - PubMed
  11.  
    1. Uusimaa J, Moilanen JS, Vainionpää 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(3):278–287. doi: 10.1002/ana.21196. - DOI - PubMed
  12.  
    1. Koga Y, Akita Y, Nishioka J, Yatsuga S, Povalko N, Tanabe Y, et al. L-Arginine improves the symptoms of strokelike episodes in MELAS. Neurology. 2005;64(4):710–712. doi: 10.1212/01.WNL.0000151976.60624.01. - DOI - PubMed
  13.  
    1. El-Hattab AW, Emrick LT, Hsu JW, Chanprasert S, Almannai M, Craigen WJ, et al. Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation. Mol Genet Metab. 2016;117(4):407–412. doi: 10.1016/j.ymgme.2016.01.010. - DOI - PMC - PubMed
  14.  
    1. Hirano M, Pavlakis SG. Topical review: mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts. J Child Neurol. 1994;9(1):4–13. doi: 10.1177/088307389400900102. - DOI - PubMed
  15.  
    1. Brambilla A, Favilli S, Olivotto I, Calabri GB, Porcedda G, De Simone L, et al. Clinical profile and outcome of cardiac involvement in MELAS syndrome. Int J Cardiol. 2019;276:14–19. doi: 10.1016/j.ijcard.2018.10.051. - DOI - PubMed
  16.  
    1. Fang W, Huang CC, Lee CC, Cheng SY, Pang CY, Wei YH. Ophthalmologic manifestations in MELAS syndrome. Arch Neurol. 1993;50(9):977–980. doi: 10.1001/archneur.1993.00540090074013. - DOI - PubMed
  17.  
    1. Vandana VP, Bindu PS, Sonam K, Govindaraj P, Taly AB, Gayathri N, et al. Audiological manifestations in mitochondrial encephalomyopathy lactic acidosis and stroke like episodes (MELAS) syndrome. Clin Neurol Neurosurg. 2016;148:17–21. doi: 10.1016/j.clineuro.2016.04.024. - DOI - PubMed
  18.  
    1. Al-Gadi IS, Haas RH, Falk MJ, Goldstein A, McCormack SE. Endocrine disorders in primary mitochondrial disease. J Endocr Soc. 2018;2(4):361–373. doi: 10.1210/js.2017-00434. - DOI - PMC - PubMed
  19.  
    1. Thakker RV. Genetics of endocrine and metabolic disorders: parathyroid. Rev Endocr Metab Disord. 2004;5(1):37–51. doi: 10.1023/B:REMD.0000016123.21743.fe. - DOI - PubMed
  20.  
    1. Afroze B, Amjad N, Ibrahim SH, Humayun KN, Yakob Y. Adrenal insufficiency in a child with MELAS syndrome. Brain Dev. 2014;36(10):924–927. doi: 10.1016/j.braindev.2013.12.009. - DOI - PubMed
  21.  
    1. Ciafaloni E, Ricci E, Shanske S, Moraes CT, Silvestri G, Hirano M, et al. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol. 1992;31(4):391–398. doi: 10.1002/ana.410310408. - DOI - PubMed
  22.  
    1. Rahman S. Mitochondrial diseases and status epilepticus. Epilepsia. 2018;59:70–77. doi: 10.1111/epi.14485. - DOI - PubMed
  23.  
    1. Rahman S. Pathophysiology of mitochondrial disease causing epilepsy and status epilepticus. Epilepsy Behav. 2015;49:71–75. doi: 10.1016/j.yebeh.2015.05.003. - DOI - PubMed
  24.  
    1. Santamarina E, Alpuente A, Maisterra O, Sueiras M, Sarria S, Guzman L, et al. Perampanel: a therapeutic alternative in refractory status epilepticus associated with MELAS syndrome. Epilepsy Behav Case Rep. 2019;11:92–95. doi: 10.1016/j.ebcr.2019.01.008. - DOI - PMC - PubMed
  25.  
    1. Finsterer J. Mitochondrial disorders, cognitive impairment and dementia. J Neurol Sci. 2009;283(1–2):143–148. - PubMed
  26.  
    1. Di Stadio A, Pegoraro V, Giaretta L, Dipietro L, Marozzo R, Angelini C. Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review. Orphanet J Rare Dis. 2018;13(1):35. doi: 10.1186/s13023-018-0770-1. - DOI - PMC - PubMed
  27.  
    1. Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, et al. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011;77(22):1965–1971. doi: 10.1212/WNL.0b013e31823a0c7f. - DOI - PMC - PubMed
  28.  
    1. Finsterer J, Wakil SM. Stroke-like episodes, peri-episodic seizures, and MELAS mutations. Eur J Paediatr Neurol. 2016;20(6):824–829. doi: 10.1016/j.ejpn.2016.08.002. - DOI - PubMed
  29.  
    1. Sue CM, Lipsett LJ, Crimmins DS, DipAud CST, Boyages SC, Presgrave CM, et al. Cochlear origin of hearing loss in MELAS syndrome. Ann Neurol. 1998;43(3):350–359. doi: 10.1002/ana.410430313. - DOI - PubMed
  30.  
    1. Koga Y, Povalko N, Nishioka J, Katayama K, Yatsuga S, Matsuishi T. Molecular pathology of MELAS and l-arginine effects. Biochim Biophys Acta BBA Gen Subj. 2012;1820(5):608–614. doi: 10.1016/j.bbagen.2011.09.005. - DOI - PubMed
  31.  
    1. El-Hattab AW, Hsu JW, Emrick LT, Wong LJC, Craigen WJ, Jahoor F, et al. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation. Mol Genet Metab. 2012;105(4):607–614. doi: 10.1016/j.ymgme.2012.01.016. - DOI - PMC - PubMed
  32.  
    1. Ihara Y, Namba R, Kuroda S, Sato T, Shirabe T. Mitochondrial encephalomyopathy (MELAS): pathological study and successful therapy with coenzyme Q10 and idebenone. J Neurol Sci. 1989;90(3):263–271. doi: 10.1016/0022-510X(89)90112-3. - DOI - PubMed
  33.  
    1. Cotán D, Cordero MD, Garrido-Maraver J, Oropesa-Avila M, Rodríguez-Hernández Á, Izquierdo LG, et al. Secondary coenzyme Q 10 deficiency triggers mitochondria degradation by mitophagy in MELAS fibroblasts. FASEB J. 2011;25(8):2669–2687. doi: 10.1096/fj.10-165340. - DOI - PubMed
  34.  
    1. Santa KM. Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Pharmacotherapy. 2010;30(11):1179–1196. doi: 10.1592/phco.30.11.1179. - DOI - PubMed
  35.  
    1. Nanau RM, Neuman MG. Adverse drug reactions induced by valproic acid. Clin Biochem. 2013;46(15):1323–1338. doi: 10.1016/j.clinbiochem.2013.06.012. - DOI - PubMed
  36.  
    1. Lin CM, Thajeb P. Valproic acid aggravates epilepsy due to MELAS in a patient with an A3243G mutation of mitochondrial DNA. Metab Brain Dis. 2007;22(1):105–109. doi: 10.1007/s11011-006-9039-9. - DOI - PubMed
  37.  
    1. Kim NH, Siddiqui M, Vogel J. MELAS syndrome and MIDD unmasked by metformin use: a case report. Ann Intern Med. 2021;174(1):124–125. doi: 10.7326/L20-0292. - DOI - PubMed

Page Navigation