Power plants collapse: Mitochondrial Diseases

Today we will talk about a unique organelle that has its own genome that can be inherited by our offspring.

Mitochondria

Mitochondria are the power plants of the cells within an organism. In a nutshell, mitochondria breakdown nutrients and convert them into energy rich molecules known as ATP. Quite remarkably, mitochondria have their own small genome (molecules of DNA that code for proteins for the production of ATP-producing complexes).

It is believed that hundreds of thousands of years ago mitochondria lived their happy independent lives. But soon they realised how much happier they would be living in a symbiotic relationship with other living cells. We as human beings are forever grateful for this relationship as it allowed us to evolve into the complex organisms that we are today.

I got it from my Mama

The genes that are coded by mitochondria (mtDNA) can only be inherited from mothers, with extremely rare exceptions. (1) In order to understand the reason behind this kind of inheritance, it is crucial to understand what spermatozoa (sperm) are. Spermatozoa are very small motile cells, whose heads are loaded with DNA. Upon entry to an egg (a considerably larger cell) the total fraction of the sperm’s mtDNA is minuscule (less than 0.1%) compared to the egg's mtDNA. On top of this, the paternal mtDNA is rapidly degraded during the early stages of embryogenesis. Therefore, genetic councillors consider the risk of paternal inheritance of mitochondrial diseases equal to zero.

Mitochondrial diseases

Mitochondrial diseases are chronic illnesses caused by malfunctioning mitochondria, which in turn leads to a range of severe symptoms. Mitochondria are found in every cell of our body, therefore mitochondrial diseases do not discriminate and affect all organs and tissues. Mitochondrial diseases can either be inherited or occur sporadically. Prevalence of mitochondrial disease in adults is 12.5 per 100,000 and about 4.7 per 100,000 in children. (2,3)

The diagnosis of mitochondrial diseases can be very challenging as their symptoms resemble other serious conditions. The symptoms include:

1. Poor growth and failure to thrive;

2. Fatigue, muscle pain and weakness;

3. Learning disabilities:

4. Autism;

5. Hearing and vision problems;

6. Seizures, migraines, stroke;

7. Gastrointestinal problems;

8. Thyroid problem;

9. Dementia;

10. Respiratory problems;

11. Problems with movements and coordination.

Currently there is no cure for mitochondrial diseases. Most treatments merely alleviate the symptoms of mitochondrial diseases, but the treatments that truly stop the progression of the diseases are largely unavailable.

Video created by the Lily foundation to explain mitochondrial diseases and the need for finding a treatment for them.

Reproductive choices for parents with mitochondrial disease

A lot of progress has been made in the field of reproductive science that help couples at risk of conceiving a baby with a fatal mitochondrial disease. One technique is called pronuclear transfer. A simplified protocol for this technique follows the following steps:

The first ever child born using this novel “three parents technique” was born in Mexico in 2016 with the help of a US-based team of scientists. The mother of the boy carried the gene of a mitochondrial disease, Leigh syndrome, which hampers the normal development of the nervous system. (4)

After vigorous debates and careful evaluation of all the ethical aspects to this procedure, the UK became the first country to legalise the licence for the mitochondrial replacement therapy. (5)

There are numerous studies trying to gain a better understanding of mitochondrial diseases and their inheritance. Hopefully, soon these diseases will find their cure.

1) Schwartz M. Vissing J. Paternal inheritance of mitochondrial DNA. N Engl J Med 2002; 347: 576-80.

2) Gorman GS, Schaefer AM, Ng Y, et al. Prevalence of nuclear

and mitochondrial DNA mutations related to adult mitochondrial

disease. Ann Neurol. 2015;77:753-759. https://doi.org/10.1002/

ana.24362.

3) Skladal D, Halliday J, Thorburn DR. Minimum birth prevalence

of mitochondrial respiratory chain disorders in children. Brain.

2003;126:1905-1912. https://doi.org/10.1093/brain/awg170.

4)Exclusive: World’s first baby born with new “3 parent” technique

Read more:https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/#ixzz6QfWgEnIp

5)Burrell C. Mitochondrial replacement therapy and ‘three‐parent children’—who should be registered as the legal parents?. BJOG: An International Journal of Obstetrics & Gynaecology. 2017 Jun;124(7):1056-.