Genetic testing results – the best possible ending to my year!

There aren’t enough superlatives to describe how happy I am that this year is nearly over. It started in March with an excruciating flare of my lymphocytic enterocolitis, and rolled into April with laser surgery on my dysplasia. A couple of days later I ended up in the ICU with hypokalaemic paralysis (which led to my CVID diagnosis). Fast forward a month and I was diagnosed with melanoma, and unrelated to this then spent 8 weeks in hospital with neutropenia and malnutrition from not being able to eat (being fed via a tube up your nose and refeeding syndrome are as horrible as they sound). Thanks to the arsenal of drugs that have kept me alive, I’ve developed osteoporosis and have spent most of the year with a “deranged” liver. On top of all this, treatment for my MS which has triggered half my problems in the first place has failed to be effective, with multiple new lesions on my brain and spinal cord. Like seriously, you can’t make this shit up.

New lesions
New lesions on my brain after 4 years of treatment, why do I bother

Despite how much trauma my body has been through (and that’s just this year!), I can’t stress enough that 90% of the time I really do feel like a completely normal and healthy person. If none of my conditions are flaring, it’s like there’s nothing wrong with me at all, for which I know I am incredibly fortunate and grateful given how terrible I sound on paper. So I was also able to do some really nice stuff this year. I went to Japan, I went on a health retreat, I had lovely trips to Canberra and Noosa, and I decided not to work at all for the rest of the year so I could focus on my health – but also so that I could go out for brunch all the time and not have to queue 😂. But perhaps nothing has been as exciting as the results of my exome sequencing.

Beautiful Japan
~ Kyoto ~

A couple of months ago I posted that the Walter and Eliza Hall Institute (a medical research institute in Melbourne) were interested in my case and wanted to look at my DNA as part of a research project (ie. free of charge). A genetic counsellor warned me that the likelihood they would find anything was slim, but it was worth a try.

So it was pretty damn exciting for me (and apparently my doctors and the scientists in the lab who discovered it too 😂) to find out the genetic mutation which has caused ALL of my problems. *Drumroll please* CTLA-4 haploinsufficiency.

Genetic results
The very smart people at WEHI and the Victorian Clinical Genetics Services worked this out. (My geneticist and immunologist don’t think I have ALPS like these results suggest though).

Over the past few weeks thanks to appointments with immunologists and geneticists and a stupid amount of Youtube videos probably intended for children, I think I’ve become a bit of an expert in genetics. It turns out I was born with a heterozygous variant in my CTLA-4 gene. WEHI have been able to pinpoint the tiny spelling mistake that has caused such a big mess. And I mean tiny. In the 410th part of the 204,735,609th section of the second chromosome, there is a ‘T’ instead of a ‘C’, meaning that in this position, the amino acid leucine is created instead of proline. That’s it. This absurdly small spelling error means that my body either doesn’t produce enough of or produces a faulty version of the protein called CTLA-4.

The CTLA-4 protein functions as a “brake” to slow down or decrease the action of the immune system. The action of a healthy immune system needs to be able to both ramp up and slow down, much like a car controlled by gas and brake pedals. CTLA-4 mutations affect multiple immune cell types and can lead to both autoimmunity and immunodeficiency.

CTLA-4 deficiency is a rare disorder that severely impairs the normal regulation of the immune system… characterized by infiltration of immune cells into the gut, lungs, bone marrow, central nervous system, kidneys, and possibly other organs.

– National Institute of Allergy & Infectious Diseases (US)

Reading case reports of the handful of other people in the world with CTLA-4 haploinsufficiency is like reading the story of my life. For the first time ever, all of my conditions fit neatly into a profile of a disease. The mystery of ~me~ is literally solved. The manifestations of CTLA-4 haploinsufficiency are the immune system attacking the central nervous system (my MS), lungs (my interstitial lung disease), gut (my lymphocytic enterocolitis), blood (my neutropenia/thrombocytopenia/lymphopenia) and paradoxically at the same time as being overactive, causes a type of combined immunodeficiency (my body struggles to create antibodies/immunoglobulins and I have reduced and poorly functioning B-cells and T-cells, the combination of which has caused chronic infection and malignancy).

Of course knowing what precisely is wrong with me is not as freaking miraculous as the fact that it can be treated. There is a drug on the market for Rheumatoid Arthritis sufferers called Orencia (abatacept), which is effectively a synthetic version of CTLA-4. This mutation was only discovered in 2014, and from all of my reading (I have literally read every journal article I can find that mentions CTLA-4), it seems that there are less than 100 people in the world identified with this problem. Of course the incidence is likely to be much higher than this but unfortunately most people do not have access to genetic testing. My neuro suggested that there could be a whole group of people whose MS is also caused by the same genetic mutation (science hasn’t yet worked out what causes MS), but without affordable and accessible genetic testing we’ll never know 🤷‍♀️. But I digress, the point is, because CTLA-4 haploinsufficiency/deficiency has been diagnosed in so few people, there is not enough of a basis for abatacept to be on the PBS for anything other than RA. Without assistance, the drug (which I will be on for the rest of my life if it works) would cost me a cool $25k a year 😳. So my immunologist is working with the Monash drugs committee to get the hospital to pay for it for me. As I write this it has unofficial approval, so hopefully I will be starting soon!

Orencia (abatacept)
The first dose of Orencia is an infusion and after that it is a weekly subcut injection

Obviously with such a small patient group there have been no Randomised Controlled Trials or other such studies into the efficacy of abatacept as a treatment for this mutation; the only evidence is anecdotal and scarce, but all the same it sounds promising for autoimmune conditions. For reasons I don’t understand there is a theoretical risk it could make my MS worse, and for reasons I do understand it could cause the melanoma to proliferate (the treatment for metastatic melanoma patients aims to DESTROY their CTLA-4 rather than increase it 😳) so I will have close surveillance for the first while and hopefully *touch wood* all will be fine!

I guess my biggest point in writing this blog was to say how bloody weird it is the way things turn out, I really feel like I have come full circle this year. This year my life has been defined by hospitals, horrible procedures and worrying about my future. Whilst it has taught me some important lessons, I know I am so much more than this and am looking forward to my disease/s taking the back seat to my life. I can’t wait to start this drug, go back to work and be Morgan 2.0 who only worries about normal people problems.


Massive thanks to my friends and family for getting me through this year, and also to the chronic community – in particular the MS community for all your support. Have a happy and safe Christmas! Here’s to a healthy 2018 for EVERYONE!

Morgan xxx

Footnote.  Morgan set up a Facebook community support group for those suffering with CTLA4 haploinsufficiency.  Please visit if you would like to touch base with or share experiences with others that are afflicted with this condition.

5 thoughts on “Genetic testing results – the best possible ending to my year!

  1. Wow what an incredible read that was! You have been on a roller coaster to hell & back this year and yet you still take time to update everyone with your posts and blog. Thank you. I hope 2018 is a year of happiness, health,success and massive adventures 💗


    1. I also have the CTL4 Mutation. Diagnosed twice. 2014 & 2018. I have been sick my whole life. People simply thought I was depressed or a hypochondriac. I have been house-bound for decades, since my teens really. I would like to talk to other people who have this genetic deficiency to compare experiences.
      Michael P Bucciarelli


      1. Hi Michael. It’s Morgy’s dad here. Sorry I am a bit late in responding to your comment (I am a bit backward in the techno skills and only just saw it). Morgan took the initiative in setting up a Facebook page for CTLA4 sufferers. Cheers Peter


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