POLG-Related Mitochondrial Depletion Syndrome
There are many medical-lingo resources out there about POLG (check them out under the tab “Mito Resources”), but I wanted to give an easy-to-understand introduction for those of you just receiving a diagnosis, or if you want something to share with friends and family to help them understand.
Almost all our cells have mitochondria, which function sort of like the energy center for that cell; some people use a battery analogy. Healthy mitochondria die just like cells do, but a healthy person’s body can always make more to power cells. Powerful cells lead to powerful body systems, and damaged cells cause damage to systems.
There are lots of types of mitochondrial diseases, and so the symptoms can vary dramatically from person to person: Some infants die within days of birth from their disease, while other people may live a relatively normal life and not even know they have it because their symptoms are so mild. Generally, though, the systems that need the most energy to operate — the brain, eyes, liver, digestive tract and so on — are usually the first and most severely affected when a person has mitochondrial disease.
Mitochondrial diseases can be caused by faulty mtDNA, a specific type of DNA that codes for mitochondria and is inherited from just the mother. They can also be caused by mutations in certain nuclear DNA genes, which can be inherited from either the mother or the father. Most of these second types are "autosomal recessive" in inheritance, meaning you have to get one bad allele from your mother and one from your father in order to inherit it.
POLG is a nuclear gene we all have. Every gene has a job, and POLG’s job is to code for mitochondrial replication; in other words, it tells the body to make more mitochondria. POLG is the only piece of our DNA that can do that, so it’s extremely important because without a functioning POLG gene, your body's store of healthy mitochondria won't be able to keep up with the energy demands it takes to live a healthy, typical life. Mutations to POLG cause what is known as a “mitochondrial depletion syndrome” because the body doesn’t know how to make more mitochondria and its store of effective cell batteries begins to deplete.
POLG mutations can result in all kinds of major health problems, depending on which mutations a person inherited from their parents. POLG specialists usually classify people into different disease categories depending on how their symptoms progress. These include Alpers-Huttenlocher syndrome, childhood myocerebrohepatopathy spectrum, myoclonic epilepsy myopathy sensory ataxia, ataxia neuropathy spectrum, progressive external ophthalmoplegia and others. But these are just boxes used to help doctors understand what to expect, and some patients kind of fall into a gray area that isn’t clearly definable or doesn’t really fit the mold of any of these specific diseases.
The most severe cases of POLG-related mitochondrial depletion syndrome cause death in early infancy, often from liver failure. Other people live longer lives, but most experience seizures, extreme fatigue, susceptibility to illness, liver disease, and a range of other issues. Like other types of mito, there is no cure and treatment is limited to dietary changes, lifestyle changes like more sleep and less strenuous activity, and supplements called the mito cocktail.
Our geneticist explained that POLG diagnosed in childhood is typically fatal in childhood; if it's diagnosed later, it’s typically less severe. But every case is unique. There are also research studies in progress on gene editing, mitochondrial implanting, and more effective supplements and drugs, that hopefully will one day provide hope for people with POLG related mitochondrial disease.