Mitochondrial diseases - Leber Hereditary Optic Neuropathy - Genetics & Biochemistry

Summary

In this video, Metagosa delves into hereditary mitochondrial diseases, focusing on Leber hereditary optic neuropathy. The video explains the role of mitochondria in energy production, how mitochondrial DNA is inherited from the mother, and the impact of mutations in mitochondrial DNA. It highlights the progressive vision loss in Leber's neuropathy, which affects central vision, leading to bilateral blindness in the second or third decade of life. The discussion also touches on the variable expression of mitochondrial diseases and the organs most affected, such as the brain, heart, and eyes, emphasizing the importance of understanding these complex genetic conditions.

Takeaways

• 😀 Mitochondria are essential for energy production in the body, especially in high-energy organs like the brain, eyes, muscles, and heart.
• 😀 Mitochondrial diseases are inherited maternally, meaning only the mother passes down mitochondrial DNA to her children, not the father.
• 😀 Hereditary mitochondrial diseases, such as Leber hereditary optic neuropathy, affect the electron transport chain, particularly Complex I.
• 😀 Mitochondrial DNA has a higher mutation rate than nuclear DNA due to weaker proofreading mechanisms.
• 😀 Leber hereditary optic neuropathy causes progressive central vision loss, starting with central scotoma and potentially leading to bilateral blindness.
• 😀 The expression of mitochondrial diseases can vary, with some patients experiencing mild symptoms and others more severe forms, a phenomenon known as variable expressivity.
• 😀 Mitochondrial diseases can affect multiple organs due to their energy needs, particularly the optic nerve, retina, heart, and nervous system.
• 😀 These diseases are more commonly seen in males than females, though the reason for this gender disparity is unclear.
• 😀 Diagnosis of mitochondrial diseases often occurs in the second or third decade of life (ages 20-40).
• 😀 Unfortunately, there is currently no cure for hereditary mitochondrial diseases, and the conditions are typically irreversible.
• 😀 Additional symptoms of mitochondrial diseases can include tremors, multiple sclerosis, and various cardiac arrhythmias.

Q & A

What are mitochondrial diseases, and how are they inherited?

Mitochondrial diseases are caused by mutations in the mitochondrial DNA, which affect energy production in cells. These diseases follow a mitochondrial pattern of inheritance, meaning they are passed down from mother to offspring, but not from father to offspring.

Why do mitochondrial diseases primarily affect the brain, eye, optic nerve, heart, and muscles?

These organs are highly active and require a lot of energy (ATP) to function. Since mitochondrial diseases impair ATP production, these organs suffer the most due to their high energy demands.

What is the role of the mitochondria in the cell?

Mitochondria are responsible for producing energy in the form of ATP through oxidative phosphorylation, which occurs in the electron transport chain.

How does mitochondrial DNA differ from nuclear DNA?

Mitochondrial DNA is inherited only from the mother, while nuclear DNA is inherited from both parents. Additionally, mitochondrial DNA has a higher mutation rate compared to nuclear DNA due to less robust proofreading mechanisms.

What is variable expressivity in mitochondrial diseases?

Variable expressivity refers to the different severity of symptoms experienced by patients with the same mitochondrial disease. Some individuals may show a typical, severe form, while others exhibit a milder version of the disease.

What is Leber hereditary optic neuropathy (LHON)?

Leber hereditary optic neuropathy is a mitochondrial disease that leads to degeneration of the optic nerve, causing vision loss, particularly central vision, which can progress to bilateral blindness. The disease is more common in males.

What is the typical age range for the onset of symptoms in LHON?

Symptoms of Leber hereditary optic neuropathy usually begin in the second or third decade of life, which is between the ages of 11 to 40 years.

What causes the central vision loss in LHON?

In LHON, the degeneration of the optic nerve leads to damage in the retina's sensory layer, resulting in the loss of central vision, starting with a condition called central scotoma.

What is the significance of the electron transport chain in mitochondrial diseases?

The electron transport chain is essential for energy production in cells. In mitochondrial diseases like LHON, mutations in components of this chain, such as complex I, impair ATP production, affecting energy-hungry organs like the optic nerve, brain, and muscles.

Why can't a father pass mitochondrial diseases to his children?

Since mitochondrial DNA is inherited only from the mother, a father cannot pass down mitochondrial diseases to his children. The sperm’s mitochondria are left outside the ovum during fertilization.