Understanding the challenges facing families seeking diagnosis for a rare condition, often called the diagnostic odyssey, is crucial, says CamRARE, the Cambridge Rare Disease Network. A diagnostic odyssey is described as the time is taken between when a symptom or feature of a genetic or rare disease is observed to the final diagnosis.
The waiting game
The average waiting time for a final diagnosis is currently estimated to be around five years and can involve the input of, on average, 4-5 doctors. But it can often take much longer, or result in being unable to diagnose. For many families, navigating their child’s diagnostic odyssey can be a long and painful journey. Trying to find answers to why their child presents with specific characteristics and health conditions and trying to understand what is causing them can be difficult, time-consuming, and a trying process that takes its toll. Danielle and her husband know all about this. It took them over four years to obtain a diagnosis for their son Reuben and they met many different consultants along the way. As Danielle explains:
“Reuben had his first testing at less than 6 months old – neither of these gave us or the doctors any answers. At this point, Reuben was referred to Great Ormond Street Hospital. We first met in July 2019, when Reuben had just turned one. In February 2020 Reuben had bloods taken for Whole Exome Sequencing (WES) This returned a normal result. There are many challenges that come with having a child with an undiagnosed condition. There is guilt, isolation, frustration, and stress, amongst many other emotions. From very early on in Reuben’s life we began to feel isolated and alone, that we didn’t ‘fit in’. Without a diagnosis it was very difficult to answer questions about Reuben.
Not being able to find the answers is a frustrating process for families. Numerous clinic visits, hospital stays, and tests that still seem to provide no definite answer make the diagnostic odyssey a traumatic one for many families as they attempt to manage a child’s symptoms without knowing their cause and the best way to support them.
The burden of care
We had an appointment with the geneticist every 6 months, so that she could be updated on Reuben’s development, and find out whether any new medical complications had arisen that may give her more clues. Reuben’s geneticist was very clear from the start that we may not find the answer to Reuben’s difficulties for a number of years, and potentially never.
Danielle D Sansum
New technology, new hope
For those who have experienced a diagnostic odyssey like Danielle, advances in genomics – and especially whole genome sequencing offer hope. Whole genome sequencing, WGS, is a laboratory technique in which the entire coding and non-coding regions of the genome are obtained. It provides a comprehensive map of a person’s genetic makeup and allows extensive analysis of all genes. The hope is that the speed of genomic technology advances will continue to increase and provide families with an answer. Danielle was delighted to finally get a diagnosis for Reuben.
For those who have experienced a diagnostic odyssey like Danielle, advances in genomics – and especially whole genome sequencing offer hope. Whole genome sequencing, WGS, is a laboratory technique in which the entire coding and non-coding regions of the genome are obtained. It provides a comprehensive map of a person’s genetic makeup and allows extensive analysis of all genes. The hope is that the speed of genomic technology advances will continue to increase and provide families with an answer. Danielle was delighted to finally get a diagnosis for Reuben.
In May 2021, when genetic testing was becoming more readily available on the NHS, Reuben was deemed suitable for Whole Genome Sequencing, to be carried out at East Genomics in Cambridge. This was the test that gave us the diagnosis.
Danielle D Sansum
What’s in a name?
For the family it meant that they had a name- the condition is called OTUD5-related neurodevelopmental disorder. They learned it is a relatively recently discovered disorder, and there are less than 50 known cases worldwide. Reuben is the only person currently diagnosed in the UK. It also meant that they could understand Reuben and the difficulties he will face as the diagnosis provided them with a list of commonly associated complications. For Danielle, it also helped her look to the future.
She explained ” We want Reuben to be happy in life, for the good days to outweigh the bad, and more than anything we want him to learn how to effectively communicate with others, in whatever form that might be. We know that Reuben’s condition is lifelong, but we now know how to explain Reuben’s presentation to others, and it should mean we can easier access care and support services when needed in the future. “
How CamRARE can help
CamRARE wants to support more families such as Danielle’s and have a lively and growing community for families living with rare and undiagnosed conditions called Unique Feet. Jo Balfour, Managing Director, explains why giving families the space to come together is important
Danielle echoes this:
” What is so fantastic about Unique Feet is that it gives children and young adults opportunities that they may not necessarily experience otherwise, and for us as parents, it allows us the space to feel completely relaxed – there are no looks from others when Reuben falls to the floor when he becomes overwhelmed – everyone is in the same boat, everyone understands. which is why it’s so important that these types of support groups exist.”
Rare Disease Day on February 28 gives those directly affected, their families and medical teams a chance to share the positive stories that are emerging, and add their voices to help find solutions to the challenges ahead.
CamRARE will join the global rare disease community to mark Rare Disease Day on February 28, calling for equitable access to diagnosis, treatment, health and social care, and opportunity. The charity hopes the campaign – supported by the Cambridge Independent – will accelerate the implementation of the UK’s Rare Disease Framework launched in 2021 and achieve earlier, more accurate, and sensitively delivered diagnoses.
Parents from CamRARE’s Unique Feet (UF) group vouch for the difference genetic testing can make. Mum Stacey Buwert said: “We had her genetic results really early; within a few weeks of her being born, we knew there was something genetic going on, but it wasn’t what they thought it would be, so it was definitely good to know.”
Mum Kym Ellis agrees, saying: “I’ve always known that there was something he needed support with, and I’ve had to basically fight the last two years for somebody to see that. We saw the geneticist who was lovely, amazing, and they said, ‘Yep, he’s got a genetic condition. We don’t know what it is, but I can just tell by looking at him and pointing out these features to you that, yes, it will be something genetic’.
“So, we’ve done the first blood test for chromosome microarray and Fragile X, and then we’ll do the whole genome sequencing.”
But how do you diagnose when there are more than 10,000 rare diseases? CamRARE says recognition among healthcare professionals that rare diseases are collectively common and that people living with rare diseases face unique challenges is an excellent place to start. Daring to ‘think rare’ is fundamental to improving the diagnostic odyssey, and CamRARE believes this, coupled with access to new diagnostic tools, can help medics spot rare diseases earlier.
Jo Balfour, managing director of CamRARE. Picture: Keith Heppell
“We are using and introducing new technologies to test patient samples to identify the cause of their rare disease and clinical symptoms,” she says. “We are translating new techniques, tests and analysis methods alongside using the latest understanding of new genes and disorders.
East GLH (Genomic Laboratory Hubs) provides genetic testing for patients in the East Midlands and East Anglia for rare disease and cancer
“We use big databases of genetic data from population and patient cohorts worldwide. These resources help clinical scientists interpret a new genetic variant we have identified in a patient. We ask: ‘Has this genetic variant been seen before in another patient with similar clinical symptoms?’ If the answer is yes, then it is likely that this genetic variant is the cause of the patient’s disorder.
“Introducing new technologies and analysis methods with increased data sharing worldwide helps provide more genetic diagnoses to patients.”
Moving from academia to the NHS, Kate takes part in national discussions to improve and standardise genomic services and improve patient pathways.
“And why do I love doing that? I am in this role to provide the best possible service for patients and their families right now, but also importantly to bring in new technologies, processes, and knowledge into the laboratory to improve testing strategies in the future.”
Cambridge Rare Disease Network talks to Karen Whitehead about the challenges of parenting, living and working with a rare disease diagnosis within the family.
Kate Whitehead was 28 when she was told that she had Pregnancy Associated Osteoporosis which is a very rare form of osteoporosis, sometimes leading to extreme bone mass loss. In most women, osteoporosis will partially or fully recover spontaneously after the pregnancy. For Kate, it meant decades of living with an invisible disability. Osteoporosis literally means ‘porous bones’ and can be a severely disabling disease. Each year it causes hundreds of thousands of hip and other fractures in the UK alone. For Kate, it meant also that she had additional worries about being able to be a good parent or if she could consider any future pregnancies. Even more worrying was what would it mean for Kate’s daughter. Kate explains
“What is also unknown, is the impact on our children, of this bone disease. Addenbrooke’s hospital also took on my daughter as a patient, when a dexa scan showed she had osteopenia in her 20s”.
Kate was very fortunate in being referred to the Addenbrooke Hospital under the Metabolic Bone Disease Unit where she remains a patient to this day. As advances in genetic testing become more available this can provide much-needed support to families. Kate was delighted to be able to take advantage of more available testing and treatments.
“Addenbrookes enrolled us both in their GEL genetic research and also the UK’s 100,000 genome research project. However, although I was incredibly worried when she fractured after a fall recently, all our family were delighted to hear that her latest dexa showed she had normal bone density for her age. The impact on our children of this rare disease remains unknown, but where most cannot obtain dexa scans, my daughter’s latest medical information has truly given hope to so many other PAO mums & their children”.
For me, the wheel has now come full circle, my daughter is newly married and I am looking forward to becoming a grandmother. Now, thanks to Addenbrooke’s hospital care, I will be able to pick up and cuddle my grandchildren and play with them – to do things with my grandchildren I was unable to with my own child.
Karen Whitehead
Rare disease patient
Whilst Kate and her husband have moved to be nearer to their daughter, she has maintained long-distance Addenbrooke’s hospital support which is still very important for her and her family.
Sadly, Pregnancy Associated Osteoporosis continues to remain a rare, unknown disease. However, there is now progress being made to better understand this debilitating condition and offer hope to new mums. For the first time in 30 years, there are two major new UK research projects, the Royal Osteoporosis Society funded project at the University of Edinburgh and also the Royal National Orthopaedic Hospital in-house funded project. Furthermore, PAO is also now included in the Rare Undiagnosed Disease Study study of rare bone diseases, by the University of Oxford. These research projects will set the future for better detection, prevention and care. Kate fully recognises this importance.
“I believe that Addenbrooke’s hospital Rare Bone Disease Clinic has one of the largest clinical groups in the UK of patients with pregnancy-associated osteoporosis and they are fully supporting the new research and helping their patient participation, by arranging blood tests and providing patient data to the research teams. I recently met up with some of the young mothers with this disease, when I was last in Cambridge for my annual clinical consultation. It was so upsetting to learn these young mothers are still facing a terrible diagnostic odyssey, over 30 years since I was diagnosed with such difficulty. This particular rare disease truly needs to be diagnosed quickly, to prevent further harm to both mothers and their babies.”
Addenbrooke’s is also supporting the Pregnancy Associated Osteoporosis group of patients and Cambridge Rare Disease Network, in currently trying to raise awareness about this condition. At present, there is a new campaign being held around Rare Disease Day 2023.
Pregnancy is normally a time of excitement for mums to be. But for some, it is a catastrophic event due to a rare condition called pregnancy-associated osteoporosis (PAO). As Karen Whitehead, herself felt.
‘27 years ago, I was about to have my first baby. My husband and I were excitedly anticipating our new family life. Instead, I experienced back pain during the last few weeks of pregnancy and my spine collapsed in labour, leaving my back broken in four places and me three inches shorter. However, nobody in the hospital would believe anything serious was wrong and I was discharged home 24 hours after giving birth’
When we think of osteoporosis, we often associate the condition with older members of our society, rarely expecting pregnant women to be affected. PAO is a severe type of osteoporosis that arises during pregnancy, after delivery, or during breastfeeding. Women lose some calcium from their bones during a normal, healthy pregnancy and breastfeeding. But in women with PAO, that calcium loss leads to significant bone fragility, particularly in the vertebrae. They can have spine or other fractures with little or no trauma. It is so rare that clinicians currently understand so little about PAO. Indeed, research on what could cause bone fractures during pregnancy is still very much in its infancy, with many cases going undiagnosed or prompting further investigation due to the condition’s rarity.
Clinicians do not know how many women have it and for many obstetricians they will never have encountered women with it, making for a challenging diagnostic pathway when a woman presents with PAO.
In the most common scenario, PAO is discovered after a pregnant or breastfeeding woman complains of severe back pain, and imaging reveals multiple vertebral fractures. Most of these women would not have had a bone assessment before this happens, and there is often a considerable delay between the onset of symptoms and diagnosis.
Karen is one of these women who aged 28 had a spinal collapse whilst in labour. She found herself in a situation where not only could she not look after her baby but struggled to be believed and like others with this condition Karen explains her frustrations.
“A terrible diagnostic odyssey, with hospital staff, midwives, health visitors and my GP refusing to believe my husband and myself that anything was wrong. My husband insisted we had to change GP and thankfully our new GP listened, believed us and started testing. But they had never heard of Pregnancy Associated Osteoporosis (PAO) and so were not testing or looking for it. Eventually, though an x-ray revealed spinal fractures, my back broken in different places, from labour and trying to lift my baby. Even seeing the x-ray, my GP queried had I ever been in a car crash or had any back injury previously.”
Women with PAO and vertebral fractures may have excruciating back pain, which can make it difficult to function and even more difficult to care for a baby. Women may also have other types of fractures that require urgent care. Aged 28, Karen was told that she had the bones of a 99-year-old woman and she was not allowed to hold, lift or carry her baby, for medical fear of new fractures.
“‘Parenting with a new, disabling, painful, rare condition was incredibly difficult over the years. This particular bone disease has a huge mental health impact, from birth trauma to the feeling of failure as a mother, the impact on career, finances, and relationships, the horrific change in body shape arising from vertebral fractures and the ongoing fear of fracturing and living with huge amounts of pain’
Karen Whitehead
Rare disease patient
Karen found herself living a restricted life and had a long period as a wheelchair user, her family living constantly in the shadow of this frightening and debilitating disease. There is no mutually agreed opinion or guideline in the treatment of this condition and Karen found herself moving around hospitals and specialists, still without a treatment plan that would work for her. At the age of 50 she was still struggling physically and mentally.
“After 20 long years of this, I was approaching 50 and the menopause – the age when women usually get osteoporosis and break bones. In that immediate post-menopause period, women can lose up to 20% of bone and one in two women aged over 50 have osteoporosis and fracture. I’d already lived with severe pregnancy-associated osteoporosis for twenty years. I was already having ongoing easy fragility fractures. I was terrified of the future and the menopause”.
Luckily for Karen help was at hand, in the shape of Dr Ken Poole. Dr Ken Poole is a University Lecturer and honorary consultant rheumatologist at the University of Cambridge, who applies novel imaging techniques to investigate human bone diseases. Research in his bone group focuses on osteoporotic fragility fractures and osteoarthritis by examining the bone structure and shape in health and disease. Karen became and continues to be a patient at Addenbrooke’s Hospital under the Metabolic Bone Disease Unit, Dr Poole was able to direct Karen towards a new bone treatment and for the last ten years, this team has supported Karen through the menopause and beyond. Prescribing and advising on various ongoing bone treatments, some of which they have been instrumental in developing. Karen is delighted to be in a much better position and is excited that,
“From having the bones of a 99-year-old age 28, I am now 60 and my bones are now those of a 60-year-old. I have not had a single fracture, since being taken on by Addenbrooke’s amazing Hospital as a long distant patient”
Put over 150 passionate and motivated people together to talk about rare disease research and you can expect a fascinating evening.
That’s just what happened at the recent public evening, hosted by Cambridge Rare Disease Network in collaboration with the NIHR BioResource for Translational Research at Addenbrooke’s Hospital to mark International Rare Disease Day 2019.
Short research talks were followed by a Q+A panel facilitated by Dr. Gemma Chandratillake, CamRARE Trustee (pictured left)
Fullagendaandbiographiesfrom the day. Click on the links below to view the audio and presentation slides for each talk.
Welcome Address Prof. Patrick Chinnery NIHR BioResource Co-Chair, Head of Department for Clinical Neurosciences, University of Cambridge
Improving Patient Health in CNO and SAPHO Dr. Jagtar Singh Nijar NIHR Clinical Lecturer in Rheumatology, University of Cambridge
Whole Genome Sequencing for susceptibility to infectious disease Dr. James Thaventhiran Consultant Clinical Immunologist, University of Cambridge (slides and audio not available)
CamRARE and NIHR Cambridge Bioresource team collaborate to host a Cambridge rare disease day lecture event #ShowYourRare
Rare Disease Day takes place on the last day of February each year. The purpose is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on the lives of those affected.
Since its launch by EURORDIS and its Council of National Alliances in 2008, thousands of events have taken place throughout the world reaching hundreds of thousands of people and resulting in a substantial of media coverage.
Following on from 2017, the theme for RDD is once again research. There has been great progress in rare disease research, often driven by effective collaborations between companies, researchers and patient advocacy groups. Click here to find out more about the vital role patients play in the research process.
Together, CamRARE and the Cambridge NIHR Bioresource team created a programme of short talks to showcase some of the ground-breaking research being undertaken in Cambridge into a range of rare conditions.
The theme of rare disease day 2018 is research. The best research translates findings into meaningful health outcomes and involves patients at all stages.
#showyourrare#whywedoresearch
Snow didn’t stop play…
Despite the snow and chilly temperatures calling for a cosy evening in on the sofa, the rare disease community came out in force to celebrate Rare Disease Day 2018 at the Uni of Cambridge School of Clinical Medicine, William Harvey Lecture theatre. Dr. Mike More, Chair of Cambridge University Hospitals, opened the evening for an exciting mix of attendees: those living with rare disease and their family members; young health professionals and students; clinicians; company and charity representatives working in related fields and the curious. Those gathered were treated to excellent presentations about current research from a wide range of speakers based on the Cambridge Biomedical campus and in the city. See the agenda opposite for info on speakers and their talks.
We used Glisser technology at the event to encourage the audience to get involved and engage with speakers by posing questions, responding to polls and sharing slides via social media. For the speaker responses to delegate questions please see here
Kay and Jo at Addenbrookes concourse meeting the staff and public
Some of the CamRARE team headed to Addenbrookes to celebrate Rare Disease Day 2018 by meeting patients, visitors and staff with other rare disease advocates at the concourse.
CamRARE’s Kay Parkinson and Jo Balfour took shelter from the snow to spend a busy few hours with other charities and departments from CUH chatting to patients, visitors and staff at Addenbrookes concourse in celebration of Rare Disease Day.
We’re always amazed by people’s curiosity, their personal stories and the knowledge we can share and gain from these kinds of interactions. Thanks for stopping by!
It was a great opportunity to let people know about our joint CamRARE/NIHR BioResource lecture event later that evening too. Read our next blog post to see who our guest speakers were.
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