‘You can carry on or give up’: Families living with rare diseases

What happens when your child is diagnosed with a disease so rare that few doctors understand it?

Daniel Lewi with his daughter Amelie [Photo courtesy of Daniel Lewi]

Daniel and Patricia Lewi were worried about their 15-month-old daughter Amelie. She had begun crawling and babbling like any other child her age but abruptly stopped. Other than that, she had a healthy appetite and was “beautiful and absolutely perfect” to her parents. “We thought it very strange for a child not to do something once they had started, so we took her to the doctor,” says her father Daniel, now 39.

In 2011, Amelie was referred to the Lewis’ local hospital in South London on the suspicion that she had a brain tumour. Multiple tests were carried out, including one to examine the back of her eye for the presence of a cherry-red spot.

Then, two weeks later, a bombshell was dropped on the Lewis: Amelie had Tay-Sachs, a rare and progressive neurodegenerative disease affecting just one in every 320,000 people. Caused by the lack of an enzyme that enables the clearance of waste in the brain, Tay-Sachs is exceptionally cruel in that it gradually destroys the nervous system and kills the individual. Although there are juvenile and adult variants of the disease, most cases occur from infancy and patients die in childhood. There is currently no cure.

“We were in our late 20s, in shock, thinking, ‘what am I being told?’” Daniel recalls. “You have no idea what the future will be, you’re told your daughter will end up completely reliant on you for 24-hour care, lose all ability to function independently, and she’s probably going to die by the age of five. And you can’t do anything to stop it. What makes it even harder is that the child is just sitting there, looking at you and smiling.”

The family went through a hellish time for weeks and then decided to get to work. “It’s really sad, but Patricia and I said we could either bury our heads in the sand and let it be awful for however long it was going to be until Amelie dies, after which it was always going to be awful anyway. Or we could try and do something positive,” Daniel says.

Amelie Lewi with her siblings Seth (now 4) and Grace (now 8) [Photo courtesy of Daniel Lewi]

Through a professor in Cambridge who specialised in research on Tay-Sachs, the Lewis started reaching out to other families affected by the disease. They hoped to share stories and experiences, provide support to one another, and look together at patient data that could be compiled and used to kick off clinical studies, which might, in turn, drive the development of potential treatments.

Four months after Amelie’s diagnosis, the Lewis set up the Cure and Action for Tay-Sachs Foundation (CATS), aimed at supporting patients and families affected by Tay-Sachs and Sandhoff disease, another ailment that is clinically almost indistinguishable from Tay-Sachs.

The encroaching awareness that any treatment they worked on would never be ready in time for Amelie was distressing. “We got the structure into place, spoke to contacts in pharma … You set up a charity thinking you’re going to save your child, and then you realise you can’t,” Daniel says. “You can either carry on or give up, but for us, it was never just about Amelie. It was about the community and all these other families.”

The stories of the Lewi family and several others are testaments to a movement of people making extraordinary strides in shaping medical approaches to rare diseases.

Individually rare, collectively common

The trials undergone by the Lewis are pervasive among people who have grappled with a rare disorder. Uncharacteristically, Daniel and Patricia were spared the long and agonising wait for a confirmed diagnosis that is endured by most rare disease patients and their families. But they found themselves having to navigate the daunting task of gathering information about their daughter’s condition, which was little understood by doctors.

Rare diseases are defined by the UK’s Department of Social Care as affecting fewer than one in 2,000 people. Though this figure implies a small patient population per disease, there are in fact more than 7,000 rare disorders, and new ones are continually being discovered. The number of patients in the UK with such diseases exceeds 3.5 million, and the equivalent global figure is approximately 400 million. Usually life-threatening or severely deleterious to quality of life, 80 percent of these illnesses are caused by genetic abnormalities, with no approved treatment for 95 percent of them.

Orphan drugs, which are a class of medicines and treatments that treat rare diseases, are also notoriously expensive: The annual cost per patient is about $147,000. For ultra-rare illnesses (with a prevalence of fewer than one per 50,000 people), the average cost per year is $750,000.

“There is a big debate from a public policy perspective about whether these prices are justified,” says Paul Martin, a professor of sociology at the University of Sheffield whose research interests include the clinical and commercial development of genomics and gene-editing technology. “The controversy is where patient groups and academics put in a lot of money into developing these drugs, but the [pharmaceutical] companies still charge really high prices.”

A diagnostic odyssey

Aside from the steep costs associated with treatment, it takes on average five to six years for rare disease patients to receive a diagnosis in the UK. During that time, patients might see up to eight doctors, and be dismissed or misdiagnosed several times. Due to a lack of knowledge and resources on the part of healthcare providers, patients and their caregivers are often at a loss about how to manage their condition even after diagnosis. The onerous, frustrating process of seeing multiple physicians who cannot get to the root of the patient’s problems is also typically referred to as “the diagnostic odyssey”.

Andrew Wakelin waited for more than 20 years before he was finally diagnosed at the age of 30 in 1980 with McArdle disease, a metabolic disorder resulting from the deficiency of an enzyme that produces the energy needed for exercise. Patients tire easily during physical exercise, reporting muscle pains and cramps. Now 71, Wakelin says the doctor who finally diagnosed him thought he was the 50th known patient in the world at the time. The incidence of McArdle disease is believed to be one in 100,000.

“I’m a typical case, even though people get diagnosed earlier today,” says Wakelin, who is now the coordinator for McArdle patients within the Association for Glycogen Storage Disease (AGSD). His earliest memories are from when he was about three or four, being unable to keep up with his older siblings while going up a hill near the family home. “In secondary school, I remember that my legs would start to hurt whenever I played tag or touch with my friends … I could never run fast enough to catch anyone.”

Andrew Wakelin on a mountain walk, with his walking poles for support [Photo courtesy of Andrew Wakelin]

Even walking uphill was a struggle for Wakelin, who describes himself as “a very solitary child” who did not meet up with any of his friends outside of school. “It’s difficult when you’re not diagnosed, but especially when there’s visually nothing wrong with you.” He was told by physicians he had an array of different issues, from growing pains to rheumatism.

It was completely by chance that his dentist – who also happened to be trained in rheumatology – noticed him limping, and suggested he take a blood test for creatine kinase (CK). Increased levels of CK generally indicate muscle damage; Wakelin’s results were off the charts.

After 25 years of having his symptoms brushed aside, Wakelin could finally put a name to what he was going through. Until 2019, he frequently attended a specialist clinic in an English town bordering Wales to try and identify potential patients and provide any support needed. Today, he still heads a patient liaison panel for McArdle patients in the UK. “I’ve also written a pocket-sized book of 101 tips for patients, which didn’t exist before, and we’ve got it translated into eight different languages,” he says.

While there is no known panacea to the disease, managing and regulating one’s movements can improve the lives of McArdle patients substantially. Wakelin says his chosen career as a typographic designer has helped him to avoid straining himself unnecessarily.

An avid walker, he has scaled all 188 mountains in Wales and traversed the length of it with two others to raise awareness of the disease. “Contrary to what some doctors might say, McArdle patients do have stamina,” he says. “It’s just the intensity we can’t do.”

Along with other representatives from the AGSD, Wakelin has carried out a training module with the Royal College of General Practitioners to help doctors diagnose McArdle faster. But the task at hand is colossal: “We’ve got around 60,000 GPs in this country, and only one in 200 is ever going to see a case of McArdle. It’s virtually impossible to educate them.”

Andrew Wakelin, at the bottom left of the photograph, on a McArdle walking course with people from seven countries in the Brecon Beacons National Park, Wales [Photo courtesy of Andrew Wakelin]

Wakelin says the typical story for undiagnosed children is that they undergo the trauma of pain, bullying and inability to keep up with their peers. “A child complaining about muscle problems should be asked to do a CK test, so the doctor knows if there’s something that needs to be seen by a specialist.”

There is also the option of genetic testing, which can check for a panel of different conditions. Sequencing the whole gene to look for defects costs about 600 pounds (roughly $800).

Twenty-three-year-old Tallulah Clark has a rare strain of ataxia, a degenerative neurological disorder that can manifest itself in a lack of balance, gait abnormality and slurred speech. It took a decade for her to be diagnosed, and she concurs that the uncertainty can be extremely alienating, especially for a child.

“Kids really aren’t the kindest at that age,” she says. “I was in the hospital practically every week … I was quiet, very insular, very different from how I am now.”

One of her symptoms was the occurrence of oral ulcers that hurt whenever she ate or spoke. A classmate teased her for having swollen lips, though she now says: “I know that it’s their problem, not mine.”

Over time, she found herself garnering the confidence to speak frankly about her ataxia. “What’s lovely is that I found that if you can be open, it also elicits that behaviour from other people.” She looks back on an incident where she had the opportunity to speak to a group of children with severe mental illnesses. “They saw that I had a walking stick and probably I was quite vulnerable in their eyes. It was rewarding to see how it helped them to share their stories.”

Tallulah Clark [Photo courtesy of Tallulah Clark]

Today, her life is full of verve and variety like most other women her age: She loves cooking, travelling to new places, learning sign language and volunteering with children who have neurological conditions. She has also just completed her undergraduate degree and is proud that she won an academic award for her dissertation, which investigates the experiences of neurodiverse individuals in the education system. While she is still learning to grapple with what she calls “brain fog” – moments where it is a strain to express herself when she cannot find the right words – she is mostly comfortable with how she has managed to slow down the progression of her ataxia. “If anyone thinks I’m not capable of doing great things, I really want to prove them wrong.”

The power of self-advocacy and community

Patients and their families often end up treading where even clinicians have not gone, steering research into therapies that did not previously exist. The efforts of these patient communities are monumental, especially considering most have no scientific training before diagnosis.

Robert Dalgleish, 67, started the charity Fanconi Hope in 2008 with two other parents of children with Fanconi anaemia (FA), a rare genetic disease that leads to bone marrow failure and heightened risk of cancer in adulthood. His daughter Louise, 20, now an interior design student at Manchester Metropolitan University, is an anomaly in that she has transitioned to adult care. In the past, when the prognosis for FA was poorer, patients were mostly seen only by paediatric haemato-oncology departments, which are concerned with the joint practice of studying and treating blood disorders and cancers in children.

Louise feels that having FA has been formative to particular aspects of her personality. “I feel like I’m [in] a rush to get things done,” she muses. “I have very different struggles from my friends … because I need to plan what I want to do, and can’t waste time doing things that aren’t useful.”

Louise Dalgleish meeting with a Scottish band called the Ninth Wave [Photo courtesy of Louise Dalgleish]

As she speaks about seeing 14 separate doctors and going for 70 screenings in one year, she exudes a sense of quiet perseverance. The enormous amount of time she has spent in hospitals has also influenced her ambition to help design facilities operated by the National Health Service (NHS), the UK’s publicly-funded healthcare system. “I want to do the small things that can make big changes. For example, making sure that every in-patient room has a window because natural light impacts how you feel day-to-day.”

The first tell-tale signs that something was wrong were the inexplicable bruises on Louise’s back when she was seven. Both her teachers and parents were concerned that she might have been hit or abused, but she could not tell them how she got the bruises. A few doctors’ referrals later, it was suspected that she had leukaemia, but blood tests later confirmed the FA diagnosis.

“I used to think my doctors were vampires,” smiles Louise, “because they always wanted my blood.” Robert, on the other hand, calls the diagnosis “the worst time of my life”, given that nobody else in their circle had a clue what FA was.

“We told people that she [Louise] had FA, and they’d go, ‘oh, but anaemia is not that bad!” adds his wife Jeannie, 60.

Bob and Jeannie Dalgleish at the Rare Disease Day Reception at the Houses of Parliament, 2020 [Photo courtesy of Bob Dalgleish]

The couple has no clinical experience: Robert is an engineer and Jeannie is a teacher. They embarked on the arduous journey of seeking help for their daughter, flying to the US for an annual conference attended by leading doctors and researchers in the disease. “It definitely helped to speak to people who knew the ropes,” Jeannie says.

Enlisting the involvement of “experts in the food chain who don’t normally talk to each other”, Fanconi Hope has helped to fund and organise an international FA working group. Its aim is to create an action plan for gene therapy trials. The charity has also convinced a few specialists to come on board as trustees: These include a medical geneticist and a paediatric haematologist.

At the end of last year, Fanconi Hope was able via its fundraising efforts to raise 92,000 pounds ($127,000) for a three-year study into proton beam therapy for FA patients who have cancer. Despite the very high risk of cancer, people with FA currently have few treatment options aside from surgery. This is because chemotherapy and radiotherapy pose significant harm to the surrounding tissue around the cancerous regions.

“We couldn’t get a grant from the normal sources because the research we fund benefits only a really small number of patients,” says Robert. “But when your kid’s life is on the line,” he adds, “there’s nothing you wouldn’t do.” At present, he believes there are about 200 individuals in the UK with FA, although the true number is unknown.

The presence of these patient groups has also been a source of solace and comfort to other families undergoing the same experience. Sam (who only wants to be known by her first name) is the mother of six-year-old Rowen, who has FA. She came across the Fanconi Hope Facebook group in her early attempts to comprehend her daughter’s diagnosis and ended up going on a trip organised by the charity to Lincolnshire.

Rowen with her puppy Buddy [Photo courtesy of Sam]

“The kids got to climb walls, play on bouncy castles and were happy and entertained. The parents got some talks, questions answered, and financial and emotional support,” Sam recalls. “I never went in with the idea that I’d be making friends just because all our kids were in the same situation, but when I was there, it was really nice not to have to explain what was wrong with our child. Now I keep in touch with a couple of families, and I’ve found it’s really good to have that support.”

Daniel Lewi emphasises that running the CATS Foundation comes down to a combination of sheer willpower, the wisdom to make astute choices with regard to how to fund research, and knowing who to reach out to. “My ex-boss gave me really good advice – he said you always have to hire people smarter than you, so they can get the job done,” he says.

He is proud of the patient registry that he and the other members of CATS have compiled. “It’s entirely patient-led – all of it is reported by patients or their carers. For example, I know exactly when and where Amelie’s first seizure was – it was the 3rd of November 2011, and I was with my father having a coffee down the road.”

Given that little is understood about Tay-Sachs, this real-world data is precious. It has helped CATS to score a partnership with Kantar Health, a company providing data and insights to the life sciences industry. In this way, Daniel says, the patient registry has brought in income for CATS’s core activities. These include respite funding for families, equipment for children with Tay-Sachs that is not offered free under the NHS, and cover for funeral expenses. CATS has also produced a mobile app and an information pack for families that can be distributed at hospitals, so that “they feel less lonely … we can make that very bad journey a bit better”.

More importantly, Daniel hopes that the data will lead to a breakthrough in drug development for patients of the disease. “You do have power when you become an expert in your disease,” he says.

Amelie’s illness transformed Daniel’s life completely, even setting him on a different career trajectory. “I’m not a molecular biologist … I had to network with the right contacts, and keep asking,” he says. Although he used to work in finance, he shifted to a job in business development for a medical technology firm. “Now I’m involved in shaping clinical trial development for patients of other rare diseases. Without Amelie, I wouldn’t have been in this position,” he says. He also serves as a mentor for patient advocates, sharing information on the right approaches to “get things done”.

Improvements to policy

In January this year, the UK government introduced the Rare Diseases Framework, which outlined in detail key strategies to address four major challenges identified by rare disease communities all over the country. These include helping patients to receive a diagnosis faster, improving awareness of rare diseases among healthcare professionals, supporting the coordination of care across hospitals and other services, and facilitating access to specialist treatment.

For families like the Lewis and the Dalgleishes, there is hope in the knowledge that policymakers are beginning to pay more attention to them. Ron Akehurst, who is Emeritus Professor of Health Economics at the University of Sheffield, also sits on the Highly Specialised Technologies (HST) committee overseeing ultra-rare diseases at the National Institute for Health and Care Excellence (NICE). In general, NICE undertakes health technology assessments and evaluates the cost-effectiveness of any drug or therapy available in the UK. “The justification for looking at rarity in itself is an ethical one,” he explains. “If you can’t provide sufficient resources to reward companies for developing drugs for very rare diseases, then the people who get them might just miss out on the advances of science.”

Akehurst also says HST is assiduously exploring ways to incentivise and prioritise solutions for the treatment and care of rare diseases that are particularly devastating. For instance, this encompasses forms of therapy that rectify rapidly degenerative genetic defects. “Without treatment, these are lives which will be very short, or of terrible quality, or both. We’re interested in treatments that will make a dramatic rather than marginal improvement. A typical new cancer treatment might extend life by two or three months. We look at things that might add anything up to 60 years … moving patients towards pretty much living a full life.”

Rowen with a horse [Photo courtesy of Sam]

But there are still other hurdles for rare disease communities to overcome in the search for a cure. At the moment, the Dalgleishes are apprehensive about the consequences of Brexit on FA research. Many existing partnerships with European clinical networks that they painstakingly cultivated over the years have ground to a halt.

“It affects the collection of patient data,” says Jeannie. “When you have sample sizes that are so small, it always helps to look at it in the context of a larger group to make it statistically valid. And suddenly they [European researchers] are saying, you can tell us your data, but we’re not allowed to give you any results back, because you’re not part of Europe any more.”

Restoring normality

Although the lives of rare disease patients and their families are by nature unorthodox, many of them are determined to introduce as much normalcy to their lives as possible. Eight years on from her bone marrow transplant, Louise Dalgleish says she is still regularly afflicted by fatigue and has to be constantly tested for a variety of cancers. It is also not easy dealing with people who have not reacted well to her illness – especially when she became bald in the process of getting new bone marrow. “People in college who didn’t know me kind of saw me as the girl with no hair. Sometimes it’s quite isolating … like an elephant in the room. If I’m at someone’s house with a tube in my arm, no one talks about it because they’re uncomfortable. But they could just ask – I don’t get hurt by it.”

She brightens visibly when talking about her hobby, which is going to and photographing alternative rock music concerts. “It’s like being transported somewhere completely different,” she says. “I’ve experienced a lot of the complete opposite – in hospitals, there aren’t many people, maybe just a few nurses, and it’s very quiet except for beeping sounds sometimes. At a gig, it’s fun, and there’s just so much noise.” On further reflection, she adds: “If people haven’t talked to me enough, they think I’m just a girl who’s got some rare disease. But my friends know I’m more than that – I love gigs, I love photography. And that’s who I like to keep around.”

Amelie Lewi [Photo courtesy of Daniel Lewi]

Amelie Lewi passed away on a Monday evening in 2017, aged eight. Daniel was picking up his two other children from nursery and after school club when she “gave a big sigh and just went very peacefully at home, on her own terms, with her mum by her side”. He looks back lovingly on her calm, measured personality, unusual for a girl her age. “Even when she got bigger and it was hard to carry her around, she was a quiet and content child. She was always very considered even before all of this, happy to sit there observing.”

Daniel believes his daughter outlived her prognosis by five years because the family placed her in an environment of normality and love. “She was a big sister … we went to music halls, to parks, doing all the things you’d do anyway living in London. And that normality helped her to be part of the family, rather than just the focus of pure attention, with everything revolving around her.”

It has been slightly more than three years since Amelie’s death, but for Daniel and the rest of the family, the pain lingers. “You never get over it,” he says. “The only people who say it gets easier are people who’ve never lost a child. You have days that are better than some, and weeks when you feel sad but you don’t know why. You just have to embrace the fact that the sadness will always be there because your daughter died. When I think of her now, I just think of her as a beautiful young girl whose memory serves a much bigger purpose with the charity.”

When asked about his hopes for CATS, Daniel is forthcoming. “My true goal is for the charity to eventually be shut down because there’s no need for it any longer. There’ll be treatments, newborn screenings, kids are diagnosed and treated right away. We may not make it until 20 to 25 years later, although science does move very quickly. But there’s still much work to be done.”

Source: Al Jazeera