Rare genetic diseases from different points of view

As I have been looking through what there is outside the world of Academia in the area of genetics, I have been discovering and stumbling upon many things that I was not completely aware of before. One of these things is the “world” of rare genetic diseases.

We (or at least I) learn about them rather superficially in Science classes in school. Then, if you study related fields in University (Medicine, Genetics, Pharmacy, etc), you might learn some more about them. But unless you go on to work on a project or company that focuses specifically on rare genetic diseases, you will not hear much about them.

While researching literature in genetics for my PhD and postdoc projects, I stumbled upon a paper here and there on the topic. But mostly, the methodology I used required large datasets, which you don’t really get in rare disease studies. So I did not get to learn more until actually looking into companies specialized on these issues.

So while searching for companies that do genetic diagnostics, I first found out about a company called Centogene. They are putting together a very extensive database on all the rare genetic diseases out there. Then, while browsing LinkedIn, I also found out they were organizing the 13th International Rare Disease Day on 29 February 2020. And I happened to be in Berlin that weekend, so I had to go check it out.

The program listed science lectures, lectures from patients and families (and organizations aimed at advocating about rare genetic diseases), short films from the Disorder Film Festival San Francisco and musical performances (this last one was extra, not related to rare diseases).

As a scientist in the area of genetics, I did not expect to find out so much that I was not yet aware of. And this made me feel like there is still a huge gap between science and the real world. When reading papers, we (scientists) focus so much on facts, numbers, mode of transmission, modes of inheritance, genetic background, that we forget there are human beings at the other end. My biggest surprise was seeing the patients and their families give testimonials and talk about their experience. All of those present were part of organizations that aim to raise awareness, provide education for the public and physicians and build support for patients and families.

Some of the of most striking things for me were:

  • There are over 4000 rare genetic diseases (such as Adrenoleukodystrophy (ALD),Cystic fibrosis, Fabry disease, …) which means that even though some are very rare (with less than 50 individuals diagnosed worldwide), put together they amount to hundreds of thousands of people. They are often misdiagnosed. Most of the time, when they are finally correctly diagnosed, it is too late to try treatments. Most of the stories shared in common the fact that their physician knew nothing about the disease they were dealing with, so the patients and the families ended up researching and being experts in the disease. Which points to how important the organizations are for support between the different patients and families.
  • There are so many issues with health insurance. Because these conditions are rare, it means treatment and cures (once researched, tested and made available) will be extremely expensive because only a handful of people will need them. So a lot of the patients are also fighting in the political side so that there is funding for research. It sounds very common-sense to me now, but I had never realized that this is such a big problem.

At the end of the Rare Disease Day, I also ended up getting a copy of the book “Rare like us” by Taylor Kane. She is a carrier for a rare genetic disease that is linked to the X chromosome, called adrenoleukodystrophy (ALD). During her presentation at the event and by reading her book, I found out about another piece of information that is not well known (and that I hope is being updated in the biology school books and genetics reference books):

  • Females that are carriers for a X-linked disease often show symptoms, granted their symptoms are not as strong as those seen in males, but they happen. X-linked diseases are inherited through the X chromosome. Females have two copies (XX), males have only one (XY). This means that males will express the genes associated with that disease because they only have one X chromosome to express. Females might not express the defective gene, because they have a healthy copy, or might express the disease partially if both copies of the gene are expressed. In school, I remember learning that females just don't develop the disease. But more recently, I read in a paper somewhere about how some genes (not necessarily ones related to diseases) in the X-chromosome in females are expressed from the two X chromosomes, not just one. (A very visual and easy to understand example is the Calico cat colour inheritance, more about it here: http://www.bio.miami.edu/dana/dox/calico.html). So it makes sense that this would be the case with diseases.

Back to the book, Taylor Kane tells in detail her story and the story of her father — John Kane, who was diagnosed with ALD in his late forties. There was (and there is still) no cure for ALD — unless diagnosed in babies, then there are some treatments that can be tried — , so the family watched how he deteriorated over the course of around two years as this condition slowly decreased his brain function. It was very interesting to read in detail about the whole story from the point of view of family members (her mother also gives input) and herself as a carrier. The book is easy to read (can be read easily by non-native speakers, like me). She did not hold back on details, which I think it’s important. She briefly discusses that some people don’t like this. I believe it is good to hear about these type of situation from others. For example, ALD patients lose bladder control and it can lead to unpleasant accidents. I also like how she covered the topic of grieving as a child. In the second part of the book, she tells how she became involved in volunteering, advocating and starting a non-profit organization called “Remember the girls”. It was nice to see the puzzle pieces coming together in her life leading her to become an advocate to increase awareness on rare diseases. Even though the main topic of the book is sad, the way she wrote it leaves you with a sense of hope and purpose by the end.

One thing I was curious about and left me wanting to know more, was the reaction of some family members that seemed to refuse to accept that John was showing symptoms — I wonder how they came to terms with it in the end. The problem with brain related conditions, is that different parts of the brain a responsible for different abilities and sometimes they can work independently. For example, it was amazing that John could talk on the phone as if nothing had changed, but in person he would stare into space and not pay attention to conversations. Which means he could fool people from time to time into doubting he had any brain limitations.

The biggest take home message from the event and from the book is that the best approach we have now is to diagnose these rare genetic diseases early. There are several tests that are done for babies, but they vary a lot everywhere in the world. They might be hard to get or expensive, but finding out about the disease before symptoms start to accumulate is the best option to try treatments, before there is permanent damage. For some of the diseases, this early intervention might mean avoiding the development of symptoms that will shorten the life of the individual and allow them to live a more normal life. It is heartbreaking to see a mother with their child deteriorating and finding out that if they were diagnosed when they were born, this could have been addressed.

Further reading and sources:

Book “Rare like us” by Taylor Kane: https://www.amazon.com/dp/1543978819/ref=sr_1_2?keywords=rare+like+us&qid=1585136774&sr=8-2

Remember the girls — nonprofit organization: https://www.rememberthegirls.org/

Rare disease day 2020 (There will be another one next year, includes short film festival and music): https://www.centogene.com/rdd2020/berlin.html

Some of the rare disease short films from the festival available online:

Tess is not alone: https://www.youtube.com/watch?v=8w_Lejbi6sE

Menkes disease finding help and hope: https://www.youtube.com/watch?v=scQEXMyygaQ

Unconditional, Raising a Glass Child with a PACS1 sibling: https://www.youtube.com/watch?v=3tcuL7NxvRc

Finn (I didn’t find the final short film online, but there is this news piece about him): https://www.youtube.com/watch?v=-IUf8MqGL8s

Biologist focused on animal behavior, zoology, genetics and medical topics. https://linktr.ee/ferrufa

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