rare disease day 2018

The Wallace Family (Credit: Great Ormond Street Hospital Charity)

John Wallace explains how an opportunity to take part in a WGS study to diagnose his son gave answers to an undiagnosed condition
his wife had been living with for 40 years. 

 

Where it All Began

Laurie had been living with an undiagnosed disease for 40 years when Keir, now 10 years old, started showing symptoms similar to Laurie at
about 10 months old. He may have had them before but we didn’t link the two because Laurie had been told that the condition would only affect women, because of Laurie’s familial history. (Laurie?s mother, maternal grandmother and they believe great-grandmother had been affected). Laurie was treated by many different specialists in the USA where we were living, including haematology, nephrology, dermatology and others. When we moved to the UK, Laurie continued to be treated for her symptoms by the dermatologist as that was the last specialty that treated her in America.

They took numerous biopsies of lesions when she was in a flare, which showed a picture of neutrophil and eosinophilic vasculitis without true leukocytoclasis. The dermatology consultant also started taking biopsies from Keir. When Keir developed a huge swelling and marked discolouration of his penile area at around 11 months old he was admitted to the hospital.

 

Kier and Laurie’s Journey

The breakthrough really came when Keir was in the hospital this time. While the head of surgery was examining and discussing Keir?s case, the rheumatology consultant, Dr Jo Walsh, was examining another patient in the ward. She overheard our conversation and asked if she could have a look. She examined Keir and asked that they put off surgery for 24 hours to see what would happen because she suspected something else. She took blood and within 24 hours the swelling had gone down considerably and had disappeared completely within 36 hours. We were then transferred to the rheumatology
department. Over the next six years, they were treated by rheumatology. The paediatric rheumatologists sent our records to various medical conferences, we attended some in Edinburgh, where up to a hundred doctors would traipse through the room we were in to have a look. XXX

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Whole Genome Sequencing 

When nothing ever came up, we just learned to live with it. They called it an undiagnosed familial vasculitis. Eventually, it was decided that they would refer us to GOSH to see if they could come up with anything. After several appointments at Great Ormond Street Hospital (GOSH), Professor Paul Brogan told us about an open study where Keir could have his whole genome sequenced. The study was only for children but he knew that Laurie had the same symptoms and managed to negotiate with the drug company that was funding the study to test our whole family of four, including myself and my daughter. The negotiations took most of that day, and as the study was almost full, there was no opportunity for the genetic counselling that would normally be offered ahead of testing. We only had 10 minutes to decide but the decision took 10 seconds and is one we have never regretted.

 

The Diagnosis

Seven months after we supplied the blood and swabs we received a diagnosis of familial cold autoinflammatory syndrome type 2. It is an R1016Xmutation of the NLRP12 gene. We received the call from the consultant rheumatologist at the Sick Kids in Edinburgh to explain the results and tell us that Laurie and Keir were the only two cases in the UK. In fact, there were only 12 cases globally. She explained there were only three academic papers related to the disease and gave us copies of them.

We were ecstatic at getting a diagnosis. We finally had a name for it. It was real.

 

Moving On

We had millions of questions and very few answers. I had never read a medical paper in my life before then and I had a totally new language to learn. It took about six months of research but eventually, I understood the meaning and context of each word in those three papers. Next, I signed on to Researchgate and started following
the authors of those papers, authors of anything to do with the NLRP12 gene in humans and mice, FCAS2, and autoinflammatory. I wanted to find others and am now in contact with patients or parents of patients around the world who have been genetically diagnosed with the condition. Most have come through Facebook and the amazing Autoinflammatory Alliance in San Francisco. One has come through
the website I run for the disease. Being diagnosed has brought us into the world of orphan drugs. After a couple of false starts, Keir is now on an orphan drug which manages his condition to the stage where he is able to attend school 77 percent of the time, previously around 50 percent. If we hadn’t had the testing and subsequent diagnosis we wouldn’t have had access to this.

Keir would be in more pain and would miss more school. The same drug didn’t work so well for Laurie and because it affects the immune system she got numerous serious kidney infections requiring emergency hospital attendance and has now been advised to stop the drug. On the day we got diagnosed, Keir was referred to child and adolescent mental health service (CAHMS) for assessment and advice on living with a lifelong chronic debilitating disease. He was discharged from them after the initial assessment but we have an open appointment where if we need their help we just have to call. We have open appointments for physiotherapy and occupational therapy and have been able to access equipment to support Laurie and Keir at home. Prior to being diagnosed, we had applied to the state for disability living allowance for Keir. We were turned down even at appeal, but after his diagnosis the children?s charity Kindred Scotland advised us to apply again. They helped us fill out the form and we were awarded higher rate for mobility and middle rate for care.

rare disease day 2018

Keir (Credit: Great Ormond Street Hospital Charity)

The Future

Not one thing changed in our lives except we had a name for what we had, but on receiving that diagnosis everything else changed letting us access services and treatment previously unavailable. The disease wasn’t discovered until 2009 so nothing could have helped Laurie prior to that with her symptoms but an earlier diagnosis would have saved us many years of struggle. About a year ago I was looking through all the old blood test reports that Dr Jo Walsh had given us after she met Keir and noticed that she had run genetic tests on the NLRP3 gene. At that time I didn?t understand what that meant (If this gene is mutated then the diagnosis is familial cold
autoinflammatory syndrome without the type 2). Those results had come back clear. It is amazing to see how close Dr Walsh was to diagnosing us and yet because of the rarity of NLRP12 it would take another seven years to get the answers we so desperately needed.

 


Materials provided by Congenica.