Rare diseases - not as rare as you think

Don’t be fooled by the word ‘rare’ in Rare Disease. Collectively, rare diseases are very common, with rare genetic disorders affecting 180,000 children in NSW. In developed countries, rare diseases account for 6 out of 10 childhood deaths.

While there are still many children living with an undiagnosed rare disease, the good news is that recent advances in genomic testing have resulted in an increase in genetic diagnoses. Dr Emma Palmer, a Geneticist at Sydney Children’s Hospital, Randwick, who specialises in Rare Diseases, says a diagnosis can be life changing for families of kids with a rare disorder.

“Many families experience years of searching for answers, not knowing if this disease will happen again in their family, or what the future looks like for their child. A diagnosis brings understanding, both for families, and for clinicians, along with the ability to ensure the right specialist supports for children as they develop,” Dr Emma Palmer.

The 28th February is International Rare Disease Day, an opportunity to raise awareness around rare diseases and improve access to treatment and medical representation for individuals with rare diseases and their families.

Eleanor's story

Until the age of five, Eleanor lived with an undiagnosed rare disorder. At four months old she was not meeting her developmental milestones, and by eight months it seemed she was going backwards. It was clear that she had a serious condition, but doctors weren’t able to give her family an answer.

In 2019 Eleanor took part in a world first global study headed up by geneticist Dr Emma Palmer. Through collaboration with international colleagues, Dr Palmer was able to describe for the first time the disorder CHEDDA - congenital hypotonia, epilepsy, developmental delay and digit abnormalities, a very rare genetic disorder caused by changes to the ATN1 gene on the 12th chromosome.

Eleanor was the first patient in the world to be given this diagnosis. Since then, almost 20 people worldwide have been diagnosed, and there will be more. Dr Palmer says it was incredibly rewarding to give Eleanor and her family a diagnosis

“If I can find an answer, and close the period of not knowing for families, I feel like I’m empowering them,” Dr Palmer.

Eleanor’s mum Blaise says that after several rounds of genetic testing without any success, their family was very relieved to finally have an answer.

“Not only did the diagnosis show us that Eleanor was on the right path with her therapies, it also confirmed that her condition was not inherited, which meant we could make an informed family planning decision.” Blaise, Eleanor's mum.

Blaise says that the most important part of having a diagnosis was finally knowing that Eleanor’s condition was not degenerative, or terminal. “Being able to give a child a diagnosis really does open the door to the best possible medical care for patients with rare diseases,” Dr Palmer says, “For example, doctors know now that patients with CHEDDA need to have a heart, brain and spinal scan as some patients will have complications in these areas. We also know that feeding can be a huge issue for some patients with CHEDDA so speech therapy is incredibly important for these kids.”

Joel's story

Parents, Jane and Simon Brookes, had a healthy and normal pregnancy so it was a shock to them both when their son Joel was born very unwell.

In 2004, Joel was diagnosed with an extremely rare genetic disorder called Pyridoxine-5'-phosphate oxidase (PNPO) deficiency in Switzerland. For Joel, this meant he suffered neonatal epileptic seizures and they were so severe that his parents were told that he may not ever be able to walk or talk.

“Even once Joel was diagnosed, we didn’t really know what it meant or what the future would hold as the disorder was so little understood. There was nobody we could ask and barely any literature we could read, so we had to adjust our expectations very early on,” said Mrs Brookes.

When Joel was four-weeks-old, he was intubated in the intensive care unit and the medical team decided to trial a treatment with the active form of Vitamin B6 called Pyridoxal 5’Phosphate (P5P), since one of the specialists had attended a rare diseases conference and had heard a case presented about a form of epilepsy that was responsive to this form of Vitamin B6. At the time, the family signed an ethical disclaimer to allow treatment as it wasn’t yet listed as a therapeutic substance in Switzerland. Once this was administered to Joel, he stabilised very quickly. The treatment saved his life, and he is the second oldest surviving child in the world with his disorder.

Joel remained healthy and well until he was 13. Unfortunately P5P can be toxic to the liver, and the high doses that Joel was treated with to keep him stable in his early years caused chronic liver disease. This liver damage increased his risk of cancer and in 2018 Joel was diagnosed with a tumour in his liver.

Joel underwent a liver transplant and spent nine months in The Children’s Hospital at Westmead post-transplant as safely treating Joel became very complicated due to his underlying disorder. Joel is the only person in the world with PNPO deficiency to have had a liver transplant. During his time in hospital, he learnt to play the ukulele and the guitar and even started taking nurses song requests.

Now 16-years-old, Joel is thriving and is back in the school routine. He takes daily medication every three hours but apart from this, Joel leads a normal life. Although their journey felt lonely at times during Joel’s early years, the Brookes family learnt to just take one day at a time and they look forward to a bright future for Joel.

“Even now as a teenager, treating Joel is a journey of discovery as the disorder is still not fully understood. There is real joy in sharing this journey with your child, that you learn to be flexible and resilient, and I feel it’s a privilege to be a parent supporting a child with a rare disease,” said Mrs Brookes.