What is a mitochondrial disorder:
Mitochondrial disorders are a class of rare inherited metabolic disorders that are the result of the mitochondria not functioning correctly. When mitochondria cannot work properly, the cells produce less energy. This shortage of energy can result in wide ranging impacts that can have many levels of severity and can affect many parts of the body. Organs and tissues that require a lot of energy to function, such as the brain, muscles and heart, are often the most affected.
As mitochondria are only inherited from the mother, genetic changes in mitochondrial genes are passed down exclusively from mother to child. It is important to note that these genetic changes arise naturally, randomly, and without fault from either parent. If genetic changes that result in non-functional mitochondria are present in the mother’s egg it is likely that she will pass on the condition to her child(ren).
However, it is possible to stop the inheritance of this type of mitochondrial disorder by using a specialised form of IVF.
Donor embryos can be used to prevent mitochondrial disorder:
When a woman is found to carry non-functional mitochondria in her eggs, it is still possible for her and her partner to have children that are genetically related to them with functional mitochondria. This is achieved through by using mitochondria donated from another egg.
Firstly, the mother’s egg (which contains non-functional mitochondria) is fertilised in vitro with the father’s sperm. This creates an embryo genetically related to the parents, but which still contains non-functional mitochondria. Simultaneously to this, a donor egg with functional mitochondria is fertilised, also typically using the father’s sperm, producing an embryo that is not genetically related to both parents but has functional mitochondria.
The embryonic nucleus, which contains the combined genetic material from the egg and sperm, is then removed from the donor embryo and replaced with the nucleus from the parents’ embryo using precise microsurgical techniques. This results in a new embryo, that contains the genetic material from both parents but functional mitochondria from a third person.
The reconstructed embryo is allowed to grow further in the lab for a short time to ensure it is healthy before being implanted into the mother’s uterus.
The image below is a diagram showing the mitochondrial donation pathway.
Real world use of donor embryos to prevent mitochondrial disorder:
Ten years ago, the UK became the first country in the world to authorise mitochondrial donation as a method to prevent mitochondrial disorders. Since 2017 couples at risk of having a child with mitochondrial disorder have been referred to the Mitochondrial Reproductive Care Pathway in the NHS.
Earlier this year clinicians and researchers at Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust reported the healthy delivery of eight babies conceived through mitochondrial donation. In each case, the babies, who were genetically related to their parents, had normal birth weights and were continuing to make normal developmental progress, but most importantly, they all had a very high percentage of functional mitochondria in their cells.
Full clinical trial results detailing the safety and effectiveness of the mitochondrial donation are expected when the children reach 18 months old, and this will confirm the procedure’s safety and its potential as a treatment option for families affected by mitochondrial disorder.
These researchers also provided a clinical pathway that details how mitochondrial donation can be used in practice to guide patient assessment, treatment planning, and embryo transfer, ensuring the safe and effective prevention of mitochondrial disorder in at-risk families.
How can this help other people living with IMDs:
Non-functional copies of mitochondrial genes are responsible for a range of inherited metabolic disorders, and although mitochondrial disorders are collectively common, there is currently no definitive cure for any of these conditions.
By addressing the root cause of mitochondrial disorders, mitochondrial donation offers a promising approach to prevent the inheritance pattern and represents a significant advancement in the treatment options available for people affected by these disorders.
What are mitochondria?
The human body is made up of billions of tiny units called cells, which perform many of the essential functions required for life, such as breathing and moving. To carry out these functions cells require energy. Mitochondria are specialised structures within the cells that are responsible for converting the food that we eat into to the energy needed to power these vital processes.
What is mitochondrial inheritance?
Each cell contains a ‘library’ of instructions which tell the cells what to do. These instructions, found in the nucleus, provide the blueprint to build cells and the directions to produce most of the proteins and enzymes in the cell. Proteins and enzymes perform the cells essential functions, including many of the processes that take place in the mitochondria.
However, not all of the instructions are found in the nucleus. A smaller second set of instructions exists in separate ‘library’ located inside the mitochondria themselves. These instructions provide the directions for building the remaining proteins and enzymes that help the mitochondria to function.
Genes are like single ‘books’ within these libraries and each one contains the instructions for one specific protein or enzyme, which can carry out one or a small number of essential functions. For more information on genes!
Genes located in the nuclear library have a classical pattern of inheritance.
- Genes are passed down from both parents
- The child inherits one copy of each gene from each parent
Many IMDs are caused by recessive nuclear genes, meaning the child will only develop the disorder if the copy of the gene from both parents contains genetic changes.
However, genes located in the mitochondrial follow a different pattern of inheritance.
- Mitochondrial genes are inherited exclusively from the mother
- All the mitochondria that are present in every single cell are descended from those originally present in the mother’s egg
- No mitochondria are transferred to the egg from the father’s sperm during fertilisation.
As a result, if the mother carries a genetic change in one of her mitochondrial genes, there is a high likelihood that this will be passed on to her children.
It is important to note genetic changes in both nuclear and mitochondrial genes occur naturally, randomly, and without fault from either parent.
The Lily Foundation: The dedicated patient organisation for mitochondrial disorders
For additional information about mitochondrial disorders or specialised patient support, please visit the Lily Foundation.
