Which are the causes of Leber Hereditary Optic Neuropathy?

Leber Hereditary Optic Neuropathy (LHON) is a rare genetic disorder that primarily affects the optic nerve, leading to vision loss. It is typically inherited maternally, meaning it is passed down from the mother to her children. LHON is caused by mutations in the mitochondrial DNA (mtDNA), which is responsible for producing energy within the cells.

The primary cause of LHON is the presence of specific mutations in the mtDNA. These mutations affect the function of complex I, a protein complex involved in the electron transport chain, which is crucial for energy production in the cells. The mutations most commonly associated with LHON are at positions 11778, 3460, and 14484 in the mtDNA.

Genetic predisposition plays a significant role in the development of LHON. However, not everyone with the mutations will develop the condition, and the reason for this variability is not fully understood. It is believed that additional genetic and environmental factors may contribute to the manifestation of the disease.

Gender also appears to influence the risk of developing LHON. While both males and females can inherit the mutations, males are more likely to experience vision loss. This phenomenon is attributed to the fact that mitochondria are primarily inherited from the mother, and males have a higher proportion of mutant mtDNA due to the absence of compensatory wild-type mtDNA from the father.

Age is another factor that affects the onset and severity of LHON. The condition typically manifests in young adulthood, with an average age of onset between 18 and 30 years. However, LHON can also affect children and older individuals, albeit less frequently.

External triggers may also contribute to the development of LHON in individuals carrying the mtDNA mutations. These triggers can include smoking, excessive alcohol consumption, certain medications, and exposure to toxins. These factors are thought to increase oxidative stress and impair mitochondrial function, further compromising the already vulnerable optic nerve.

In conclusion, Leber Hereditary Optic Neuropathy is primarily caused by specific mutations in the mitochondrial DNA, affecting the function of complex I and leading to vision loss. Genetic predisposition, gender, age, and external triggers may influence the development and severity of the disease. While LHON is a complex condition, ongoing research aims to uncover more insights into its causes and potential treatments.