Long-term Clinical Follow-up of Patients with A3243G Mitochondrial tRNA Mutation : Clinical Phenotype and Natural Course

Ahn, Mi Sun; Jeoung, Woo Chul; Hwang, Jin Soon; Kim, Sung Hwan

Abstract

PURPOSE
Mitochondrial disorder is a progressive disease, but there are no specific treatment modalities to prevent the progression. Also, there has been little understanding on the pattern of disease progression nor natural history. The aim of this study was to elucidate the initial clinical phenotypes, patterns of the disease progression, and its natural history of the patients with mitochondrial A3243G mutation.
METHODS
Among the patients with biochemically or genetically confirmed mitochondrial disorders, 7 patients with A3243G mutation were included in a 7 year follow-up observation(range: 3-11 years). We classified the patients into two groups by the initial clinical presentations:systemic and neurologic onset. They were clinically evaluated with serial brain MRI and MRS for the evaluation of the disease evolution patterns.
RESULTS
The clinical manifestations of mitochondrial A3243G mutation were extremely variable; seizure, headache, dementia, myopathy, sensorineural hearing loss, external ophthalmoplegia, diabetes mellitus, cardiomyopathy, easy fatigability, and short stature. Among the 7 patients, 4 patients initially presented neurologic symptom such as seizure(3) and headache(1), and 3 patients systemic symptoms such as DM(2) and easy fatigability(1). All the patients with neurologic onset showed relentless progression with recurrent stroke- like episodes and intractable seizures, and finally fell into be functionally dependent states or death. All the patients with systemic onset showed clinically silent periods for 3-10 years, and still they were in functionally independent states despite subsequent neurologic symptoms.
CONCLUSION
We could find out the relationship between initial clinical phenotypes and final outcomes in mitochondrial A3243G mutation. However, the population is small in this study so that a larger scaled analysis is needed.