This week’s blog has been written by Andrew Strong.
In his blog, Andrew explores the barriers preventing rare disease patients from accessing treatments, and how medics and researchers can improve access to treatments and trials in the future, with specific reference to Prader-Willi syndrome.
His blog was originally written for the Student Voice Prize essay competition in 2018.
The majority of rare diseases do not have a licensed treatment.
There are an estimated 7000 rare diseases [1] , which all have significant barriers to treatment, but one remains close to my heart.
I first met Jacob in 2012 as a support worker for children with learning difficulties. He was a pleasant young man of 16 and we immediately got on well. After taking him for his favourite activity of swimming I met his mother, Abigail, a
wonderful and friendly lady who makes every effort to help Jacob receive the best treatment possible and live a good life.
I then learnt that Jacob suffered from Prader-Willi syndrome (PWS). As a genetics student, this was particularly interesting to me as we had only recently learnt about this as an imprinting disorder.
It dawned on me that this was a rare disease that many doctors will never come across.
Years later as a medical student, it would be described by other students as “the one where you can’t stop eating and get really fat”. This is in direct contrast with Jacob who, thanks to Abigail’s keen and educated care and diet management, was a slim young adult of normal weight.
I took Jacob for outreach approximately once a week for a two year period and spent more time building a relationship with him than I will any patient as a doctor. The last time I saw Jacob, we watched the final Hobbit film.
I had finished my Genetics degree and left the job to focus on studying postgraduate medicine, but it was a pleasure to go out with Jacob, in his words, “not as a carer, but as a friend.”
3 years on, as a final year medical student, I sent my wishes to Jacob and Abigail and asked about their thoughts and feelings regarding the treatment of his PWS, to get a real and personal understanding of the barriers and difficulties they face. The issues highlighted also broadly apply to the treatment of rare diseases in general.
Names and some details have been anonymised to protect patient confidentiality. I also contacted the Prader-Willi Syndrome Association (PWSA) for their comments [2].
Background to PWS
Prader-Willi Syndrome is a rare genetic disorder affecting one in 8,000 – 20,000 births [3].
It is ultimately caused by a lack of expression of paternally expressed genes in the 15q11-13 chromosomal region.
One or more genes can be affected and this can occur by a mixture of aetiologies [4]. There is marked clinical variability but babies are floppy at birth with a poor suckling reflex. There is global developmental delay, cognitive disability, short stature and excessive appetite that can lead to obesity.
Treatment is not curative and involves interventions such as growth hormone treatment, food supervision and surgery for scoliosis and undescended testes.
Diagnosis
Jacob was diagnosed within 4 weeks of his birth, which according to the PWSA is fairly typical, except in cases with mild symptoms, due the accuracy of diagnostic testing [5].
However the barrier they described was the way in which a diagnosis and information was given. It is felt that the diagnosis is rarely given well as the rarity of the disease means a clinician will often simply be repeating information that has been quickly ‘googled’ five minutes prior.
Signposting to relevant charities does not occur routinely and in rare cases a diagnosis has even been given over the phone by the genetics laboratory [6] .
Abigail described the news of Jacob’s diagnosis as devastating, coming after an extremely stressful period of difficult feeding leading to nasogastric intubation and failure to thrive.
If a diagnosis is mishandled, parents can feel isolated and confused due to uncertainty or misinformation. To overcome all these early barriers, parents must be given accurate and up-to-date information that empowers them and enables them to understand what prognosis and treatment they should expect.
They need to be made aware of the charities like PWSA, which provide a sense of community, ongoing support in highly specialised issues, and up-to-date information.
Accessing treament
In addition to a poorly managed diagnosis, the rarity of PWS can lead to clinical care that is not standard practice. There can be a lack of co-ordination and coherence in management due to limited literature on PWS. For example, most children with PWS are treated with growth hormone from approximately one year of age, but some parents in PWSA report their endocrinologist not mentioning or suggesting this treatment [6].
Furthermore, even if a doctor has other patients with PWS, they may not appreciate the marked clinical variability of the syndrome and the need to tailor treatment to individual patient needs [7].
To support NICE guidance and overcome these obstacles, PWSA are producing a Care Pathway to aid endocrinologists as to the best practice and they hope for this to eventually be accepted by NICE.
An effective way to deal with these issues is through specific multidisciplinary clinics, of which there are four for PWS patients in the UK [8] . These are advantageous because endocrinologists, dieticians and community support staff with experience in PWS work in tandem to provide co-ordinated patient care.
Jacob was not one of the children fortunate enough to be born close to one of these multi-disciplinary clinics, and so effectively lost this ‘postcode lottery’. Although Abigail, as a parent, has been remarkably successful in managing Jacob’s weight to an ideal standard, she has not received the support for this that she would receive elsewhere.
Abigail became frustrated with the endocrinology team when conflicting messages were given at different times and the outcome of an appointment would depend very much on the consultant she saw. This could be overcome by opening more multidisciplinary centres for PWS.
The MRI revealed brain shrinkage at a prior stroke site, common for someone of Mary’s age. Mary was now requiring aid to walk, move and stand.
Luna felt as though no one was listening to her when she said her mum’s decline was unusual – ‘Having to challenge the medical team at every step was soul destroying’. A pacemaker insertion to treat the ‘bradycardia’ did not resolve her symptoms, proving a misdiagnosis. Parkinson’s and LBD was later ruled out, yet there was insufficient evidence to exclude anxiety, depression or dementia.
This prolonged diagnostic period only served to further exacerbate the family’s emotional suffering. It was only 3 months later when Luna self-referred her mother to the Edinburgh Prion clinic, that she finally felt she was being listened to. The team gave her family the time to explain what they had experienced, taking Mary through various cognitive assessments and tasks.
A formal diagnosis was eventually made, after a long and arduous mentally challenging eight months of uncertainty and confusion. These were the individuals that finally made a positive influence on Mary’s journey, and a referral to social services, OT and PT was promptly made.
Transitional care
A lot of these conflicts came around the time of Jacob’s transition to adulthood. This is an issue for childhood diseases in general but particularly in rare diseases and those that cause intellectual disability [9]. Paediatric clinics are more supportive and holistic in their care of patients and there can be a sudden shift into limited adult care.
Abigail described how in Jacob’s childhood, consults with the endocrinology team felt ‘nurturing’ and that there was a sense of continuity because Jacob always saw the same consultant. Even with the issues previously described, the staff knew Jacob and his personal problems and could discuss and address them. However, since he turned 18, Jacob’s care seems less ‘joined up’ and the nurturing element has disappeared due to unknown medical staff and a different style of care.
Abigail and Jacob find that they are repeating themselves to a new medical professional on a regular basis. Furthermore, when Jacob turned 18 he was taken off growth hormone but he started to experience major fatigue and a worsening of symptoms. Abigail asked for Jacob to be restarted on treatment. One team member was supportive of this but another member was opposed. She was frustrated and confused by this and eventually wrote a letter asking for a trial of growth hormones and quoting NICE guidelines to the team [10].
In the appointment following the letter, Abigail felt ‘demonised’ for asking for the treatment and thought that some people would be intimidated by the ‘us versus them’ situation. After this, growth hormone was reintroduced and Jacob’s symptoms appear to be improving.
In rare diseases in particular there is often the phenomenon of the expert patients where people have the knowledge and skills to play a pivotal role in their own management [11,12]. It is obvious that a confrontational approach, perceived or otherwise, is not conducive to facilitating this process. Clinical staff should be empathetic and open to suggestions or requests, and sensitively articulate any reasoning for not doing so. A situation should not occur in which a parent needs to study and present NICE guidelines to clinical staff!
Conclusion
In summary, I have been gifted with the opportunity to see Jacob in the context of being a support worker, a genetics student and finally a medical student. He lives a happy and fulfilled life with great family support and care from the NHS.
However, he and other PWS patients face several barriers to treatments. In particular these are: poorly explained diagnoses and patient information, lack of access to specific multidisciplinary care and a difficult transition to adult care.
However, we are already starting to see solutions to these barriers, for example through more multidisciplinary clinics, dedicated charity support and awareness from clinical staff of the difficult transition to adulthood. Through patients, their families, charities and clinical staff working together in unison, we can break through these barriers and continue to improve the lives of patients with PWS like Jacob.
I would like to thank Beacon, Jacob and Abigail, and PWSA for the invaluable experience and information that I have received. These lessons will stay with me as I embark on my clinical career.
References
1. National Center for Advancing Translational Sciences. FAQs About Rare Diseases. [Updated 2016 Aug 11; cited 2017 Nov 12]. Available here.
2. Prader-Willi Syndrome Association UK. PWSA UK. [Updated 2017; cited 2017 Nov 12]. Available here.
3. Butler, M., M. Hanchett Md, J., and Thompson, T. (2006) Clinical Findings and Natural History of Prader-Willi Syndrome
4. Angulo, M. A., Butler, M. G., and Cataletto, M. E. (2015) Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Invest 38, 1249-1263
5. Gunay-Aygun, M., Schwartz, S., Heeger, S., Riordan, M. A., and Cassidy, S. B. (2001) The Changing Purpose of Prader-Willi Syndrome Clinical Diagnostic Criteria and Proposed Revised Criteria. Pediatrics 108, e92
6. Prader-Willi Syndrome Association UK. Personal communications. Available on request.
7. Elena, G., Bruna, C., Benedetta, M., Stefania, D. C., and Giuseppe, C. (2012) Prader-Willi Syndrome: Clinical Aspects. Journal of Obesity 2012, 473941
8. Smith, C., Kanumakala, S., and Livesey, A. (2011) Monitoring progress in a multi disciplinary team prader willi syndrome (PWS) clinic – all is not always what it seems. Archives of Disease in Childhood 96, A30
9. Schrander-Stumpel, C. T. R. M., Sinnema, M., van den Hout, L., Maaskant, M. A., van Schrojenstein Lantman-de Valk, H. M. J., Wagemans, A., Schrander, J. J. P., and Curfs, L. M. G. (2007) Healthcare transition in persons with intellectual disabilities: General issues, the Maastricht model, and Prader–Willi syndrome. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 145C, 241-247
10. National Institute for Health and Care Excellence (2010). Human growth hormone (somatropin) for the treatment of growth failure in children. NICE Technology Appraisal Guidance (TA188)
11. Department of Health. The expert patient: a new approach to chronic disease management in the 21st century. London: Stationery Office, 2001
12. Budych, K., Helms, T. M., and Schultz, C. (2012) How do patients with rare diseases experience the medical encounter? Exploring role behavior and its impact on patient–physician interaction. Health Policy 105, 154-164
Thank you for reading this essay.
The winners of the Student Voice Prize 2024 will be announced on Rare Disease Day!
