The Usefulness of Muscle Biopsy in Initial Diagnostic Evaluation of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

다국어 초록 (Multilingual Abstract)

Purpose: The disease entity mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterizedby an early onset of stroke-like episodes. MELAS is the most dominant subtype of mitochondrial disease. Molecular genetictesting is important in the diagnosis of MELAS. The mitochondrial DNA (mtDNA) 3243A>G mutation is found in 80% of MELASpatients. Nevertheless, molecular analysis alone may be insufficient to diagnose MELAS because of mtDNA heteroplasmy. Thisstudy aimed to evaluate whether muscle biopsy is useful in MELAS patients as an initial diagnostic evaluation method.
Materials and Methods: The medical records of patients who were diagnosed with MELAS at the Department of Pediatrics ofGangnam Severance Hospital between January 2006 and January 2017 were reviewed. The study population included 12 patients.
They were divided into two subgroups according to whether the results of muscle pathology were in accordance with mitochondrialdiseases. Clinical variables, diagnostic evaluations, and clinical outcomes were compared between the two groups.
Results: Of the 12 patients, seven were muscle pathology-positive for mitochondrial disease. No statistically significant differencein clinical data was observed between the groups that were muscle pathology-positive and muscle pathology-negative for mtDNA3243A>G mutation. Additionally, the patients with weakness as the initial symptom were all muscle pathology-positive.
Conclusion: The usefulness of muscle biopsy appears to be limited to an initial confirmative diagnostic evaluation of MELAS.
Muscle biopsy can provide some information in MELAS patients with weakness not confirmed by genetic testing.

참고문헌 (Reference)

1 Nesbitt V, "The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation--implications for diagnosis and management" 84 : 936-938, 2013

2 Uusimaa J, "Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children" 62 : 278-287, 2007

3 Koenig MK, "Presentation and diagnosis of mitochondrial disorders in children" 38 : 305-313, 2008

4 Manwaring N, "Population prevalence of the MELAS A3243G mutation" 7 : 230-233, 2007

5 Joyce NC, "Muscle biopsy evaluation in neuromuscular disorders" 23 : 609-631, 2012

6 Pavlakis SG, "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes : a distinctive clinical syndrome" 16 : 481-488, 1984

7 Goto Y, "Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation" 42 (42): 545-550, 1992

8 Sproule DM, "Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes : basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome" 1142 : 133-158, 2008

9 Zeviani M, "Mitochondrial disorders" 127 (127): 2153-2172, 2004

10 Kisler JE, "Mitochondrial diseases in childhood : a clinical approach to investigation and management" 52 : 422-433, 2010

11 Haas RH, "Mitochondrial disease : a practical approach for primary care physicians" 120 : 1326-1333, 2007

12 Hirano M, "Melas : an original case and clinical criteria for diagnosis" 2 : 125-135, 1992

13 El-Hattab AW, "MELAS syndrome : clinical manifestations, pathogenesis, and treatment options" 116 : 4-12, 2015

14 Lorenzoni PJ, "MELAS : clinical features, muscle biopsy and molecular genetics" 67 : 668-676, 2009

15 Yatsuga S, "MELAS : a nationwide prospective cohort study of 96 patients in Japan" 1820 : 619-624, 2012

16 Rollins S, "Diagnostic yield muscle biopsy in patients with clinical evidence of mitochondrial cytopathy" 116 : 326-330, 2001

17 Parikh S, "Diagnosis and management of mitochondrial disease : a consensus statement from the Mitochondrial Medicine Society" 17 : 689-701, 2015

18 Goto Y, "Clinical features of MELAS and mitochondrial DNA mutations" 3 : S107-12, 1995

19 Parsons T, "Autonomic symptoms in carriers of the m.3243A>G mitochondrial DNA mutation" 67 : 976-979, 2010

20 Moraes CT, "Atypical clinical presentations associated with the MELAS mutation at position 3243 of human mitochondrial DNA" 3 : 43-50, 1993

21 Morten KJ, "A new point mutation associated with mitochondrial encephalomyopathy" 2 : 2081-2087, 1993

22 Goto Y, "A mutation in the tRNA(Leu)(UUR)gene associated with the MELAS subgroup of mitochondrial encephalomyopathies" 348 : 651-653, 1990