A family shows maternal inheritance of a disease with lactic acidosis and stroke-like episodes, with variable expression among members. What is the most likely genetic mechanism?

• A. MELAS
• B. Huntington disease
• C. Alzheimer disease
• D. Klinefelter syndrome

Answer: (A)

A mutation in mitochondrial DNA causing MELAS is the most likely mechanism. Mitochondrial inheritance comes from the mother, so all her children inherit the mutation, but the severity varies because of heteroplasmy—the mix of mutant and normal mitochondrial genomes within cells. Tissues with high energy demands, like brain and muscle, are most affected, leading to lactic acidosis and stroke-like episodes. This pattern of maternal transmission with variable expression fits MELAS precisely. The other diseases listed don’t show this maternal inheritance pattern or the characteristic metabolic/neurologic features.