MELAS : Clinical Features according to Genetic Characteristics

Hwang, Hee; Chae, Jong Hee; Kim, Ki Joong; Hwang, Yong Seung

Abstract

PURPOSE: This study was performed to estimate the frequency of mitochondrial DNA (mtDNA) A3243G point mutation in MELAS(mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) of our population and to identify the clinical or laboratory variables suggesting MELAS with mtDNA A3243G tRNA mutation.
METHODS
Thirty-one patients were included, diagnosed with MELAS in Seoul National University Children's Hospital between Jan. 1993 and Aug. 2002. Seventeen males and fourteen females were included. Mean age of onset was 7.66 years old and mean duration of follow-up was 4.8 years. Brain MRI was performed in all and muscle biopsy was performed on eleven cases. A3243G point mutation was analyzed by PCR/RFLP using DNA from blood and/or muscle tissue.
RESULTS
A3243G point mutation was detected in 15(15/31, 48.4%). Mean age of onset was 10.52 years old in A3243G (+) group, and 4.77 years in(-)group. Eight in A3243G (+) group and 2 in(-)group revealed the history of migraine(53.3%, 12.5%, respectively, P value, 0.015). Ten in (+) group and 4 in(-)group experienced recurrent attacks of stroke or transient ischemic attack(TIA)(83.3%, 40.0%, P value=0.02). The lactate level was significantly different between two groups; 2.39 in (+) group, 1.42 in(-)group. Additionally, stroke or TIA as an initial symptom, a history of diabetes or hearing impairment was frequently associated in A3243G (+) group. In brain MR, A3243G (+) group tended to be more frequently involved at posterior cerebral cortex than at basal ganglia. On muscle biopsy, ragged red fibers were detected in 4 patients (4/6) in A3243G (+) group, and 3 (3/5) in(-)group.
CONCLUSION
In our populations, A3243G mitochondrial tRNA mutation was responsible genetic defect in 48.3% of MELAS patients, less frequent than other populations. On clinical point of view, older age of onset, recurrent TIA including migraine and lactate concentration higher than 2 times of upper margin of reference value were highly suggestive of A3243G point mutation. MELAS is characterized by various clinical or genetic heterogeneity, so further large scale prospective study will be needed to identify the other genetic causes of them.