What happens in Leigh disease, exactly?

What is it?

Leigh disease is rare genetic disorder that mainly affects the brain and the spinal cord. The first symptoms typically appear within the first year of a child’s life, and they include things like diarrhea, vomiting and trouble with swallowing. As the disease progresses, the brain slowly looses control over the muscles. This makes the muscles weak and causes things like involuntary muscle contractions. The development of children with Leigh disease is also impaired and they often die because of breathing problems. Depending on the particular subtype of the disease this can happen very young although some children do make it to their teenage years.

Leigh disease occurs in at least 1 in 40 000 births, although as with most genetic diseases because of the genetic differences of populations, there is a much higher prevalence in some areas. For example, Leigh disease is seen in as many as 1 in 2000 births in a part of Canada.

What causes it?

Leigh disease is caused by a gene mutation. Genes are basically the instructions for building proteins, and proteins are basically the things that form us and keep all the chemical reactions inside us going.

The vast majority of our genes are stored in the nucleus which formed when the egg cell of our mother and the sperm cell of our father combined. But that’s not the whole story. We also have genes in our mitochondria, which are the tiny cell organelles that convert energy from molecules like glucose into a form the cell can use. (It’s because mitochondria probably originated from bacteria who swam inside bigger cells and stayed there! They can also divide independently which no other cell organelle can do.) About a fourth of Leigh disease cases are caused by a mutation in mitochondrial genes. This means that only the mother can transmit the mutation to future generations as it’s the egg cell that provides cell organelles like mitochondria, and the mother can transmit the mutation to all of her children. About 75% of Leigh disease cases are caused by a mutation in the “regular” genes. These mutations are recessive, which means that you need faulty copies from both of your parents to become affected.

What happens during it?

Mitochondria transfer the energy in glucose into energy molecules called ATP. To do this they first need to oxidize the glucose molecules in order to release energy from them. Several enzymes are needed in this process, and Leigh disease happens when one of these enzymes doesn’t work properly which prevents the glucose molecules from being oxidized and hence the ATP from being formed. ATP is the molecule which our cells use as their energy source, so you can probably see why this is a problem.

The cells that require a big and constant supply of energy are the ones most severely affected. In Leigh disease the cells that suffer the most are the brain cells that maintain basic functions like breathing, swallowing and blood circulation, and the brain cells that control movement and balance. Other affected cells include the heart and other muscles. These cells start to die because of the lack of energy, which leads to the symptoms of Leigh disease: loosing control over muscles, problems with things like breathing and swallowing, and eventually death.

How can it be treated?

Unfortunately, there is currently no effective treatment for Leigh disease. Sometimes a carefully structured diet can help with the symptoms. In 2016, researchers were able to help a mother with a mitochondrial mutation to give birth to a healthy child. Most of the genes are in the nucleus, and the researchers took the nucleus from that mother’s egg cell and placed it into another woman’s egg cell whose nucleus had been removed. That way the mother could give birth to a child who had almost the same genes as she did but who didn’t have the faulty mitochondrial genes. This, and the advancement of gene technology in general, give hope that women with mitochondrial mutations could be helped to produce healthy children and that even people with the disease could one day be treated.

 

 

 

Sources: https://en.wikipedia.org/wiki/Leigh_disease, https://en.wikipedia.org/wiki/Oxidative_phosphorylation, https://en.wikipedia.org/wiki/Spindle_transfer, http://emedicine.medscape.com/article/948360-overview#a5

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