MELAS with multiple stroke-like episodes due to the variant m.13513G>A in MT-ND5

Area of Science:

• Genetics
• Neurology
• Mitochondrial Diseases

Background:

• Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a common mitochondrial disorder, typically caused by the m.3243A>G mtDNA variant.
• The clinical presentation of MELAS includes stroke-like episodes, seizures, cognitive decline, and lactic acidosis.

Observation:

• A 33-year-old male presented with recurrent stroke-like episodes (StLEs) and progressive cognitive decline over 10 years, initially misdiagnosed as ischemic strokes or cerebral vasculitis.
• Cerebral imaging revealed characteristic stroke-like lesions in MELAS.
• Genetic analysis identified a rare variant, m.13513G>A, in the MT-ND5 gene, encoding subunit 5 of Complex I in the mitochondrial respiratory chain.

Findings:

• The identified MT-ND5 variant, m.13513G>A, is a rare cause of MELAS.
• The patient showed significant clinical improvement with a treatment cocktail of antioxidants and cofactors.
• This case demonstrates that StLEs in MELAS can resolve spontaneously and the disease course can be slowly progressive.

Implications:

• This case expands the spectrum of genetic causes for MELAS, emphasizing the importance of considering rare MT-ND5 variants.
• The positive response to antioxidant/cofactor therapy suggests a potential therapeutic strategy for patients with this specific MELAS-associated variant.
• Early and accurate genetic diagnosis is crucial for appropriate management and understanding the long-term prognosis of MELAS.