Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS

Area of Science:

• Genetics
• Neurology
• Mitochondrial Diseases

Background:

• Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a common multisystemic mitochondrial disease.
• The A3243G mutation in mitochondrial DNA is the most frequent genetic cause of MELAS.

Purpose of the Study:

• To investigate the longitudinal changes in A3243G mutation load in blood DNA.
• To correlate A3243G mutant loads with clinical phenotypes and functional status over time.

Main Methods:

• Studied 34 individuals with the A3243G mutation (17 MELAS patients, 17 carrier relatives) for up to 7 years.
• Quantified A3243G mutation levels using sensitive real-time polymerase chain reaction.
• Assessed functional status using the Karnofsky score.

Main Results:

• The percentage of A3243G mutation in blood DNA decreased progressively over time in both symptomatic patients (0.5%/year) and carrier relatives (0.2%/year).
• Despite decreasing mutation load, fully symptomatic patients showed worsening functional status.
• Functional status remained largely unchanged in carrier relatives.

Conclusions:

• A3243G mutant load in blood DNA is not a reliable indicator for prognosis in MELAS.
• Blood A3243G mutation levels are not useful for assessing functional status in individuals with MELAS or related conditions.