'My girl can't walk or talk': Searching for answers in Wales' rare disease cluster

Rachel Cowley's daughter Jessica was like any other 10-year-old until she started having seizures.

Now aged 20, Jessica is unable to walk or talk, and Ms Cowley fears she will die in the next few years.

"I hope when the time comes it is quick," said Ms Cowley. "But I just don't think it's going to be."

Jessica is one of a "cluster" of people in south Wales affected by Dentatorubral-pallidoluysian atrophy, or DRPLA, an inherited and progressive neurological disorder for which there is no known treatment or cure.

DRPLA was believed to mainly affect people of Japanese origin and considered rare in the UK, until a 2007 research study found a relatively high prevalence of the condition in Wales.

The symptoms of DRPLA can vary significantly, but generally include progressive memory loss and personality change, impaired control of body movements, muscle spasms, seizures and psychiatric disturbances.

It is caused by a gene defect, and a person with the condition has a 50% chance of passing it on to a child of their own.

Dr Mark Wardle, a consultant neurologist who authored the 2007 study, said there were a number of "common founders" with DRPLA in south Wales which had resulted in the current "cluster of patients in their 20s or 30s".

"It doesn't take many generations to have very many more cases just from the most common founders," he added.

Ms Cowley said Jessica was initially diagnosed with epilepsy aged 10, when she began having seizures.

"We could never control it," said Ms Cowley, 45, from Pontypridd, Rhondda Cynon Taf.

But when Jessica turned 13, Ms Cowley said her daughter's legs began to "give way".

The teenager, who previously loved doing gymnastics and horse riding, was now struggling to walk.

"I noticed that she could hardly walk up the stairs," said Ms Cowley.

"When she lost her voice, I just thought, these ain't signs of epilepsy, there's got to be something else."

After "years of wondering" why her health was deteriorating, Jessica was diagnosed with DRPLA in May.

Jessica now uses a wheelchair and is completely non-verbal.

"It's quite scary because she's been going through this for the last five to seven years," said Ms Cowley.

"I would speak to the consultant and they just did not know why she was deteriorating like she was.

"I think it's because of this disease being so rare."

Ms Cowley is part of a group called DRPLA in south Wales on Facebook, which currently has more than 100 members.

Ms Cowley said it was a "massive surprise" to find other people in her area were facing the same challenges.

"We're all connected in a way," she said.

"It's nice to talk to some of them and have advice off them, because if I phone the GP, they don't know nothing about it."

Zoe Hoes adopted her eight-year-old daughter Gabriella when she was a baby.

Last year, she was contacted by social services who said that a member of Gabriella's birth family had tested positive for DRPLA.

Ms Hoes, 47, from Cwmbran, Torfaen, noticed her daughter was twitching at night and thought she might have symptoms.

"I managed to get a private test done and that confirmed that she did have it," Ms Hoes added.

She said she was left "scrambling to find out information" about the condition.

"It's terrible because at the moment there is no treatment and no cure.

"You love them so much and you don't want to lose them."

Ms Hoes said the private test cost her "in the region of £2,000" which she acknowledged was unaffordable for many.

"A lot of families haven't got that money to spend," she said.

"So they just carry on with their lives, and anyone's child could meet someone with [DRPLA] and end up being a carer for their partner and children."

Ms Hoes would like to see more people being tested for the condition at a younger age.

"[Parents] need to be able to make plans for those children's futures because, ultimately, they're going to be caring for them," she said.

Dr Wardle began his research study into the DRPLA prevalence in south Wales after finding "several families" with the condition.

He said the DRPLA gene, also known as the ATN1 gene, was crucial in understanding the disorder.

If the gene expands in a large way "over multiple generations" a person will "probably have a more aggressive disease than [their] parent", explained Dr Wardle.

He said the current generation of DRPLA patients had, in this way, experienced "more severe disease".

"That's why it feels as if we've suddenly got more patients," he said.

"When I first found patients with this disease in south Wales, they were in their 50s or 60s.

"Now we've got a cluster of patients in their 20s or 30s and that's why we're seeing that difference."

Dr Wardle said it was "very difficult" to diagnose DRPLA because it was "astonishingly rare" compared to similar conditions like epilepsy.

"Unless you've got a family history, people aren't even going to consider it," he added.

He said raising awareness about DRPLA was a "really good thing" as it would make people think about it earlier.

"Getting good access to neurological services and genetic testing is really important to push this forward," he added.

But Dr Wardle said there were "moral and ethical issues" with testing people under the age of 18.

He said people needed to be mature enough to "understand the consequences" of being tested for the "life-changing" condition.

"You can't do that if you're six or 12-years-old.

"I know of one patient who has been devastated by being screened for this disease," he added.

Dr Wardle said it would be "very different" if there was treatment available.

"I think we'd change our approach because we want to identify those patients early.

"But that would be on the basis of early access to treatment, which we don't have at the moment."

The families affected in Wales said that clinical trials in the US for a potential treatment were providing "hope".

But Dr Wardle said these trials could "potentially" cause more harm to families by "raising expectations".

"There's a pipeline where you've got to prove safety and then prove efficacy, and you've got to do that right," he said.

Dr Silvia Prades is a research manager at the charity Ataxia UK and CureDRPLA.

She is currently working with a team based in the US who are trialling a treatment on two people living with DRPLA.

She said the early results had been positive with one of the people on the trial, a teenage boy, showing signs of improvement.

"He's now able to walk a few steps without assistance. He has regained some small movement in his hands and his speech is a bit clearer," she said.

The second patient, a woman in her 30s, was more advanced in the condition and Dr Prades said any improvement had been "less obvious".

She said the treatment effects could "vary" but felt the results were "encouraging".

Dr Prades said she understood why people wanted testing at an earlier age but stressed that it was a "personal choice".

"Some people will feel empowered by having this knowledge. Others feel a huge burden," she said.

Dr Prades said a "combination of many different factors" might explain why DRPLA prevalence appeared to be higher in south Wales than the rest of the UK.

"Perhaps it is the access to genetic testing has improved. It could also be that people are more aware of the condition," she said.

"It could also be that the stigma on genetic conditions is being removed."

She said there had been an "increase" in the number of families "engaging" with her team in recent times, which could be because people are experiencing the symptoms of DRPLA at an earlier age.