MELAS Syndrome Treatment & Management

  • Author: Fernando Scaglia, MD, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: May 3, 2010
 

Medical Care

Evaluation for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome may be performed on an outpatient basis if the patient is stable. Evaluation may consist of determining levels of serum lactate and serum pyruvate, mtDNA mutation studies on blood, and brain imaging studies (eg, head CT scan, brain MRI, brain proton magnetic resonance spectroscopy [1 H-MRS]). Muscle biopsy for mitochondrial enzymes and DNA mutation analysis can be performed as an elective procedure for which the patient is admitted to the hospital.

In incidents of acute decompensation, perform inpatient studies in the acute phase and following stabilization of the patient.

Various supportive measures are available, although no controlled trial has proven efficacy. Long-term benefits of dietary manipulations are unknown. Improvements in some patients may be related to improved nutritional status and hydration.

The following medications have been used:

  • Treatment with coenzyme CoQ10 has been helpful in some patients with MELAS syndrome. No adverse effects have been reported from its administration.
  • Menadione (vitamin K-3), phylloquinone (vitamin K-1), and ascorbate have been used to donate electrons to cytochrome c. Idebenone has also been used to treat this condition, and improvements in clinical and metabolic abnormalities have been reported.
  • Riboflavin has been reported to improve the function of a patient with complex I deficiency and the m.3250 T → C mutation. Nicotinamide has been used because complex I accepts electrons from nicotinamide adenine dinucleotide (NADH) and ultimately transfers electrons to CoQ10.
  • Dichloroacetate is another compound used with these agents since levels of lactate are lowered in plasma and cerebrospinal fluid (CSF); patients reportedly may respond in a favorable manner. Sensory neuropathy may result after extended use of this drug.
  • Sodium succinate has been used, and a patient with MELAS syndrome reportedly had fewer strokelike episodes with its use; however, sodium succinate is not the standard of care. Further investigation is necessary.
  • Creatine monohydrate has also been used, and an increase in muscle strength in high-intensity anaerobic and aerobic activities has been reported.
  • The administration of L-arginine during the acute and interictal periods may represent a potential new therapy for this syndrome to reduce brain damage due to impaired vasodilation in intracerebral arteries owing to nitric oxide depletion.
Next

Consultations

The following consultations may be indicated:

  • Geneticist
  • Neurologist (to evaluate patient for strokelike episodes)
  • Cardiologist (for evaluation of cardiomyopathy, arrhythmias and hypertension)
  • Nephrologist (to evaluate for the onset of nephrotic syndrome)
  • Ophthalmologist (to evaluate for pigmentary retinopathy)
  • Endocrinologist (to evaluate for endocrine dysfunctions such as diabetes mellitus, hypothyroidism, hyperthyroidism and hypoparathyroidism)
  • Psychiatrist (to evaluate for affective disorders)
  • Neuropsychologist (to evaluate for autism spectrum disorder [ASD])
Previous
Next

Diet

The effect of dietary manipulation is not completely known, and the efficacy of dietary supplements is unproven. Dicarboxylic aciduria and secondary impairment of long-chain fatty acid oxidation (LCFAO) may occur in mitochondrial disorders. Improvement observed in many patients is probably related to improved nutrition.

Previous
Next

Activity

In patients with mitochondrial myopathies, moderate treadmill training may result in improvement of aerobic capacity and a drop in resting lactate and postexercise lactate levels. Concentric exercise training may also play an important role because after a short period of concentric exercise training a remarkable increase reportedly occurs in the ratio of wild type–to–mutant mtDNAs and in the proportion of muscle fibers with normal respiratory chain activity.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Fernando Scaglia, MD, FACMG  Associate Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital

Fernando Scaglia, MD, FACMG is a member of the following medical societies: American College of Medical Genetics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for the Study of Inborn Errors of Metabolism

Disclosure: Nothing to disclose.

Specialty Editor Board

Edward Kaye, MD  Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD  Professor and Chair of Pediatrics, Stony Brook University, New York

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Genzyme Grant/research funds PI

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Mehrazin M, Shanske S, Kaufmann P, Wei Y, Coku J, Engelstad K. Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS. Am J Med Genet A. Feb 15 2009;149A(4):584-7. [Medline].

  2. Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 1: Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Arch Neurol. Jan 2010;67(1):19-24. [Medline].

  3. Sasarman F, Antonicka H, Shoubridge EA. 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. Dec 1 2008;17(23):3697-707. [Medline].

  4. Nemes A, Geleijnse ML, Sluiter W, Vydt TC, Soliman OI, van Dalen BM. Aortic distensibility alterations in adults with m.3243A>G MELAS gene mutation. Swiss Med Wkly. Feb 21 2009;139(7-8):117-20. [Medline].

  5. [Guideline] International Diabetes Center. Type 2 diabetes practice guidelines. 2003;[Full Text].

  6. Fayssoil A. Heart diseases in mitochondrial encephalomyopathy, lactic acidosis, and stroke syndrome. Congest Heart Fail. Nov-Dec 2009;15(6):284-7. [Medline].

  7. Betts J, Jarost E, Perry RH et al. Molecular neuropathology of MELAS; level of heteroplasmy in individual neurons and evidence of extensive vascular involvement. Neuropathology and Applied. Neurobiology. 2006;32:359-373.

  8. Borner GV, Zeviani M, Tiranti V, et al. Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients. Hum Mol Genet. Mar 1 2000;9(4):467-75. [Medline].

  9. Ciafaloni E, Ricci E, Shanske S, et al. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol. Apr 1992;31(4):391-8. [Medline].

  10. Deschauer M, Tennant S, Rokicka A, He L, Kraya T, Turnbull DM. MELAS associated with mutations in the POLG1 gene. Neurology. May 15 2007;68(20):1741-2. [Medline].

  11. Hirano M, Pavlakis SG. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts. J Child Neurol. Jan 1994;9(1):4-13. [Medline].

  12. Hirano M, Ricci E, Koenigsberger MR, et al. Melas: an original case and clinical criteria for diagnosis. Neuromuscul Disord. 1992;2(2):125-35. [Medline].

  13. Jacobs HT, Holt IJ. The np 3243 MELAS mutation: damned if you aminoacylate, damned if you don't. Hum Mol Genet. Mar 1 2000;9(4):463-5. [Medline].

  14. Joko T, Iwashige K, Hashimoto T, et al. A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes associated with diabetes mellitus and hypothalamo-pituitary dysfunction. Endocr J. Dec 1997;44(6):805-9. [Medline].

  15. Kaufmann P, Engelstad K, Wei Y, et al. Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. Feb 14 2006;66(3):324-30. [Medline].

  16. Koga Y, Akita Y, Nishioka J, et al. L-arginine improves the symptoms of strokelike episodes in MELAS. Neurology. Feb 22 2005;64(4):710-2. [Medline].

  17. Matsumoto J, Saver JL, Brennan KC, Ringman JM. Mitochondrial encephalomyopathy with lactic acidosis and stroke (MELAS). Rev Neurol Dis. Winter 2005;2(1):30-4. [Medline].

  18. 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. Oct 1984;16(4):481-8. [Medline].

  19. Pons R, Andreu AL, Checcarelli N, Vila MR, Engelstad K, Sue CM. Mitochondrial DNA abnormalities and autistic spectrum disorders. J Pediatr. Jan 2004;144(1):81-5. [Medline].

  20. Scaglia F, Northrop JL. The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options. CNS Drugs. 2006;20(6):443-64. [Medline].

  21. Shanske S, Coku J, Lu J, Ganesh J, Krishna S, Tanji K. The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases. Arch Neurol. Mar 2008;65(3):368-72. [Medline].

  22. Shimotake T, Furukawa T, Inoue K, Iwai N, Takeuchi Y. Familial occurrence of intestinal obstruction in children with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). J Pediatr Surg. Dec 1998;33(12):1837-9. [Medline].

  23. Sue CM, Bruno C, Andreu AL, et al. Infantile encephalopathy associated with the MELAS A3243G mutation. J Pediatr. Jun 1999;134(6):696-700. [Medline].

  24. Tanahashi C, Nakayama A, Yoshida M, Ito M, Mori N, Hashizume Y. MELAS with the mitochondrial DNA 3243 point mutation: a neuropathological study. Acta Neuropathol. Jan 2000;99(1):31-8. [Medline].

  25. Tay SH, Nordli DR Jr, Bonilla E, Null E, Monaco S, Hirano M. Aortic rupture in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes. Arch Neurol. Feb 2006;63(2):281-3. [Medline].

  26. Thambisetty M, Newman NJ, Glass JD, Frankel MR. A practical approach to the diagnosis and management of MELAS: case report and review. Neurologist. Sep 2002;8(5):302-12. [Medline].

 
Previous
Next
 
Pathophysiologic classification of lactic acidosis.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.