Which are the causes of MELAS Syndrome?

MELAS syndrome, which stands for Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, is a rare genetic disorder that affects the mitochondria, the energy-producing structures within our cells. This condition is caused by mutations in the mitochondrial DNA (mtDNA) and is typically inherited maternally, meaning it is passed down from the mother to her children.

Mitochondrial DNA Mutations: The primary cause of MELAS syndrome is the presence of specific mutations in the mtDNA. Mitochondria have their own DNA separate from the nuclear DNA, and these mutations can disrupt the normal functioning of the mitochondria, leading to the symptoms associated with MELAS. The most common mutation associated with MELAS syndrome is the m.3243A>G mutation, which affects a gene called MT-TL1.

Energy Production Impairment: Mitochondria play a crucial role in producing energy in the form of adenosine triphosphate (ATP) through a process called oxidative phosphorylation. However, in individuals with MELAS syndrome, the mitochondrial mutations impair this energy production process. As a result, affected cells and tissues do not receive an adequate supply of ATP, leading to energy deficiency.

Lactic Acidosis: One of the hallmark features of MELAS syndrome is the presence of lactic acidosis, which refers to the buildup of lactic acid in the body. Lactic acid is a byproduct of anaerobic metabolism, which occurs when the cells cannot produce enough ATP through oxidative phosphorylation. The impaired energy production in MELAS syndrome leads to an increased reliance on anaerobic metabolism, resulting in the accumulation of lactic acid.

Stroke-like Episodes: Another characteristic feature of MELAS syndrome is the occurrence of stroke-like episodes. These episodes involve neurological symptoms similar to those seen in strokes, such as sudden onset of weakness, seizures, vision and speech problems, and altered consciousness. The exact cause of these stroke-like episodes is not fully understood, but it is believed to be related to the impaired energy supply to the brain, leading to dysfunction and damage in certain areas.

Other Contributing Factors: While mitochondrial DNA mutations are the primary cause of MELAS syndrome, other factors can influence the severity and presentation of the condition. These factors include the heteroplasmy level, which refers to the proportion of mutated mtDNA in a person's cells, and the tissue distribution of the mutations. The heteroplasmy level can vary among different tissues and organs, leading to variations in symptom severity and the specific organs affected.

Genetic Inheritance: MELAS syndrome follows a maternal inheritance pattern due to the presence of mtDNA mutations. This means that affected individuals inherit the condition from their mother, as the mitochondria and their DNA are primarily passed down through the maternal line. However, the severity and age of onset can vary even among family members due to differences in the specific mutations and heteroplasmy levels.

Conclusion: In summary, MELAS syndrome is caused by mutations in the mitochondrial DNA, leading to impaired energy production, lactic acidosis, and stroke-like episodes. While the exact mechanisms behind these manifestations are not fully understood, the impact on cellular energy supply and mitochondrial dysfunction play a central role. Understanding the causes of MELAS syndrome is crucial for diagnosis, management, and ongoing research to develop potential treatments for this rare genetic disorder.