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Rebekah and her son Edmund went through a diagnostic odyssey to find the cause of Edmund's symptoms

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A bout of strep throat was the start of a diagnostic odyssey. The discovery of a rare genetic variant led to an effective therapy.


Edmund’s rare genetic variant uncovered a life-changing treatment

As a 19-year-old uni student living in Canberra, Edmund knew something was wrong. He was suddenly always tired, constantly out of breath and started getting severe body aches.

A first visit to the GP diagnosed strep throat, but when antibiotics didn’t help, more tests were done. They showed an abnormally large spleen, severe liver cirrhosis and low blood count. Doctors suspected a form of cancer, but no diagnostic tests could confirm this, or point to a treatment.

“I was 19 years old, and doctors told me I had the liver of a 40-year-old alcoholic,” says Edmund. “As time went on, the ‘unknown’ factor, and the symptoms, were just getting worse and worse.” Doctors were doing what they could to find the cause, but they came no closer and a liver transplant was fast becoming the only option for Edmund.

After seeing four other specialists, Edmund’s case was referred to Professor Tri Phan, co-lead of the Precision Immunology Program at Garvan and immunologist at St Vincent’s Hospital Sydney.

By chance, Professor Phan had read a research paper that reported a variant in the 

 gene, which produced overly active immune molecules that cause recurring infections and damage to organs. At the time, there were just nine patients worldwide found to be carrying this gene variant.

“The penny dropped when Edmund’s mother Rebekah told me she had been diagnosed with Behcet’s disease – an autoimmune condition with unknown cause. From there, a genetic test revealed that several members of the family had inherited this 

“I was so relieved when the search was over. We knew then that it was an autoimmune condition, and there were things that could be done about it,” he says.

On compassionate grounds, Edmund received a monoclonal antibody therapy called adalimumab, usually used to treat rheumatoid arthritis, which blocks the molecule that was overly active in Edmund. His symptoms quickly receded. While his therapy is not a cure, today Edmund lives a normal, active life and next year he will head to Oxford University to embark on a PhD in mathematics.

“Having the genetic diagnosis brings the peace of mind that any additional symptoms I start experiencing would be monitored closely and taken seriously,” says Edmund.

Edmund’s mother Rebekah and two of Edmund’s siblings also carry the altered 

 gene. Rebekah was prescribed adalimumab and is managing her rheumatoid arthritis symptoms better than previously, and while his siblings have no symptoms, this early genetic diagnosis gives them immediate options should symptoms start occurring.

Primary immunodeficiencies are rare individually, but together they are quite common – over 6 million people globally are affected by over 430 conditions. 

“The more we look, the more we find,” says Professor Phan. “We are trying to move to a more personalised model of care for patients, rather than trying a one-size-fits-all approach.”

While an effective treatment for Edmund was quickly found, many patients with primary immunodeficiencies are not so lucky and suffer through diagnostic odysseys for years. But researchers from Garvan and St Vincent’s Hospital Sydney are working to put a stop to this.  

Garvan’s Associate Professor Elissa Deenick and St Vincent’s Dr Alisa Kane are leading the TheraPID study, which is measuring the outcomes of precision therapies in patients with primary immunodeficiency. As part of this, the team is developing new tests for immune function that will allow them to better measure treatment response and thereby tailor treatment more precisely to individual patients to correct their immune imbalance. Through this, the team hopes to make life-changing personalised treatment available to more patients.

“Patients with primary immunodeficiencies often have few places to turn. We are finding that personalised care has better outcomes for individuals, and we want to implement this widely so that more patients can benefit,” says Associate Professor Deenick.

“Genetics-driven personalised care for primary immunodeficiency has been a game changer for many of our patients with treatment resistant disease. We are beginning to see better health and better quality of life,” says Dr Alisa Kane.

Professor Tri Phan is a Conjoint Professor at St Vincent's Clinical School, Faculty of Medicine and Health, UNSW Sydney. Associate Professor Deenick is a Conjoint Associate Professor at St Vincent's Clinical School, Faculty of Medicine and Health, UNSW Sydney.