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[00:00:12] Dr Karolina Stepien: Hello and welcome to this third webinar of the webinar series Shine a Light on Alpha- mannosidosis, a Brighter Future. Next slide, please. Here's the disclaimer. So the educational webinar is brought by Chiesi Global Rare Diseases. And all this content is focused on disease state. And the presentations will not include information about specific treatments or medications. And it is a webinar for health care professionals only. Next slide, please. So some housekeeping notes, as usual. So please don't take screenshots or don't reproduce any of the slides, content, or images. We will have a question and answer session at the end of the webinar. So please submit your questions at any time via the question and answer button in text only. And we will answer the questions after the webinar presentations. And the webinar will be recorded and will be available on demand later. So what are the learning objectives of today?
[00:01:29] Dr Karolina Stepien: First, we want to understand how to consider approaches to treatment- related follow- up care, including therapies like ERT, HSCT, or supportive care, and how timely access to treatment may improve patients' outcomes. We would like to discuss also to demonstrate the need of a multidisciplinary approach to care and how this may be tailored to the individual. And the third for today is to discuss challenges and also hopes for the future of care in alpha- mmannosidosis and how the Delphi recommendations should help guide care. Next slide, please. The agenda is, after this welcome and introduction, we will have a presentation about optimizing treatment- related follow- up and care. The next one is the multidisciplinary approach to care. And this will be also with case reports. And then the future of care in alpha-mannosidosis, a panel discussion between the three of us. So the faculty today will be Dr. Barbara Burton from the Children's Hospital of Chicago in USA. There will be Dr Karolina Stepien from Salford Royal Hospital in UK. And my name, Christina Lampe. I'm working at the University of Gießen in Germany. So here are our disclosures. And I will not go into detail. And for the wrap- up, what we discussed in the last webinars. So what we know from alpha-mannosidosis is that we have a wide range of symptoms that are associated with this disease, like cognitive impairment, behavioral problems, hearing impairment, et cetera. But individuals with alpha-mannosidosis may present with different symptoms at different ages. And this is a topic we would like to discuss also today. Next slide, please. We know that these clinical manifestations and this broad spectrum of manifestations place a high burden on patients and caregivers. For patients with alpha-mannosidosis, it's the impaired mobility, for example, pain or the psychological impact. But also, we have a big burden on caregivers, like anxiety, depression, social life, financial burden, et cetera. So it's really a disease that is not only focused on medical, but also on psychological and social issues. So the Global Delphi Consensus Study has provided the first best practice guidance for health care providers. And the three key areas focus on assessments and newly diagnosed individuals, routine follow-up care, and treatment-related follow-up care. And this will be our big topic for today. So, and with this, I give the stage to Barbara Burton, talking about the optimizing treatment related follow-up care.
[00:05:15] Prof. Barbara Burton: Oh, thank you so much for the introduction, Christina. It's my pleasure to join you on the webinar today to discuss the topic of follow- up care. Whoops, I got a little too speedy with the slide controls. Let me try to go back. Whoops, seems to be very sensitive at my end, but here we are. Okay, so there are two types of therapy for alpha-mannosidosis that we would consider disease-modifying therapies, and that would be hematopoietic stem cell transplantation and enzyme replacement therapy, but then, of course, supportive care is important for all patients, and there are certainly some patients who may receive only supportive care. When HSCT is considered, it should be considered as early as possible in life, ideally in the first decade, and it's primarily indicated to preserve neurocognitive function and prevent early death in those patients who have the rapidly progressive severe form of the disorder. The risks and benefits, of course, like any therapy, should be discussed with the patient before this is considered. Enzyme replacement therapy is generally well tolerated. There are some risks, but not quite as complex as we see with HSCT. Of course, it is regarded as a standard treatment, and it has been shown in clinical trials to improve both biochemical and functional parameters in affected patients, but the long- term outcomes are still to be elucidated. Supportive care covers a vast range of things in patients with alpha-mannosidosis because the clinical manifestations, as you've heard, are so variable and involve many different organ systems. We have to pay attention to whether there is immunodeficiency, and if so, we use standard therapies for immunodeficiency for treatment and prevention of infections.
We need to monitor cardiac and respiratory issues, and some patients certainly have psychiatric manifestations that require monitoring and treatment. If a patient has hearing loss, of course, we would use hearing aids. Some patients are treated with bisphosphonates like Pamidronate for osteoporosis. And therapies such as occupational and physical therapy can be very helpful. Of course, orthopedic care may be needed because of the skeletal involvement, and as we heard from Christina about the burden of treatment and of the clinical manifestations on both patients and family members, attention really to the psychological needs of the patient and of the caregivers is very important. With counseling, social work, psychological intervention when needed and helpful for the patient. So let's focus a little bit more on the patients who have had hematopoietic stem cell transplantation and monitoring really specific to this treatment modality. And biochemically, we can monitor the efficacy of treatment by measurement of serum and or urine oligosaccharides, and of course, monitoring whether transplant has been successful in restoring normal circulating enzyme activity in leukocytes, which is typically where it would be measured. We also want to, of course, monitor a patient for other symptoms of alpha-mannosidosis over time, even if a patient has had a successful transplant, because we know that transplantation, while certainly ameliorating some of the symptoms, prolonging survival, and stabilizing neurocognitive decline, may not address all of the symptoms of the disease. So we need to continue to see the patient annually, and when I say we, I mean the metabolic physician or geneticist. These are patients who are also going to be monitored for transplant- specific complications, typically by a transplant team, but I think the role of the geneticist or metabolic physician is still very important in the patient, even following transplantation.
The transplant team will monitor the patient for complications like GVHD, ensure that there is full and lasting engraftment, and things of that nature. So what about patients who undergo enzyme replacement therapy? Again, we can look at the efficacy of treatment biochemically by monitoring the serum and urino- oligosaccharides , so looking at substrate clearance, if you will, and this can be done obviously with blood and urine tests. I think it's appropriate that we do this pre- enzyme replacement therapy and then subsequently every 6 to 12 months. Because enzyme replacement therapy involves giving a large protein, we also have the possibility of development of antibodies to the enzyme, so antibody titers should be monitored, particularly in patients who develop infusion- related reactions or have evidence of insufficient clinical response to therapy. In other words, the oligosaccharides don't decrease as you would expect and or you don't see clinical benefit in the patient. If a patient does have infusion- related reactions, these can be treated with use of pre- medication and or slowing of the infusion. Many times patients who experience reactions will get over them over time, so it's rare that a patient could not continue therapy, but some modification of how it's administered may be necessary. And then, of course, these patients also need comprehensive symptom- based monitoring, just as was true for the transplant patients, so they need to be seen and assessed once a year for complications of the disorder in the various organ systems that have been discussed in previous webinars.
Now, in terms of supportive care, as we discussed, there may be patients who don't undergo either transplant or have ERT but receive supportive care only, and just as the patients who do receive the disease- modifying therapies, they need to be regularly monitored every 6 to 12 months, again with symptom- based assessments and some of the routine assessments of the various organ systems that we've discussed where we can see clinical involvement. We know that with HSCT, there are complications that can occur. I mean, death is certainly one that's not listed here, but there is mortality, of course, associated with HSCT, but also long- term complications like GVHD, endocrine disorders, pulmonary complications related to the chemotherapeutic agents that are used for conditioning, similarly some CNS complications. Our main complications that we monitor with regard to ERT would be, again, the infusion- related reactions. That's really the main thing that we observe, which can include hypersensitivity, including even anaphylaxis, and certainly commonly less severe reactions like urticaria, arthralgia, and so on. So let me share with you the case of a patient who I've had the pleasure of following for close to 20 years now. This is a child who began having symptoms in the first year of life. As an infant, this child had multiple hospital admissions between 7 and 11 months of age for reactive airway disease, and a chest x- ray at 10 months of age revealed skeletal findings suggestive of dysostosis multiplex. He was also noted at about 11 months of age to have hepatomegaly. So based on both of those findings, the child was referred to a geneticist who suspected an MPS disorder and obtained urine glycosaminoglycans, which were normal. At that point, a liver biopsy was recommended for further evaluation. The parents at that point sought a second opinion with a hepatologist at our institution in Chicago and at that time, the physical exam revealed coarse facial features, frontal bossing and a broad nasal bridge. The liver was enlarged. It was palpable five centimeters below the right costal margin and the spleen five centimeters below the left. There was a lumbar kyphosis and mild hypotonia. So it's easy to understand why someone would have suspected an MPS disorder in this case and the hepatologist seeing the patient certainly suspected a storage disorder of some type and referred the patient to me at that time. We again repeated the urine gags which were normal and obtained urino οligosaccharides which were abnormal and a lysosomal enzyme panel revealed deficient alpha-mannosidosis activity confirming the diagnosis of alpha- manocytosis. The patient clearly had a severe phenotype having developed symptoms in the first year of life so HSCT was recommended. This was performed at 17 months of age using the HLA identical mother as a donor. The patient became fully engrafted. There was no acute GVHD but he did develop chronic graft-versus-host disease with skin, eye, and mucosal involvement.
Other issues that were observed over the ensuing years included chronic otitis media, he had ear tubes placed at four years of age, multiple dental caries requiring multiple restorations under general anesthesia, and he continued to experience developmental delay and had some behavioral issues early in childhood. As time went on, his condition really appeared to be relatively stable. He had stable intellectual impairment, mild to moderate intellectual impairment. His behavioral issues gradually resolved over time. As he got into his teens, however, he began to experience decreased mobility going from having been able to walk say a mile to being able to walk only a block without needing to rest and he also began to experience some joint pain. So about a year ago, he was started on enzyme replacement therapy at the age of 19 years and the patient has since then reported improvements in joint pain and improved mobility. He has not had abnormal immunoglobulins at any time since transplant. They've been monitored periodically. His immunoglobulins have been normal. His cardiac assessments have been normal as well. So, that's his story and I'll turn it back to you now, Christina, for our discussion.
[00:18:55] Dr Karolina Stepien: Thank you so much, Barbara. It's an impressive case in particular over this long time of observation. How was the patient followed up? Was there any standard or?
[00:19:11] Prof. Barbara Burton: Yes. Well, we didn't have guidance from the literature, of course, 19-20 years ago, but following his transplantation, I continued to follow him on an annual basis. We obtained periodic echocardiography and ECG to monitor his cardiac status. We obtained skeletal x-rays on several occasions and he does have some skeletal changes, but none that have required any orthopedic intervention. I have monitored his immunoglobulins periodically and those have continued to be normal. And of course, I've done a routine physical examination and looking for findings on exam as well. He has had hearing assessments and his hearing is normal at this point. So, I think, you know, all of that suggests that he has had some benefit from the transplant.
[00:20:20] Dr Karolina Stepien: What is most impressive for you in this case?
[00:20:27] Prof. Barbara Burton: I think a couple things. One is I believe that he showed us over time the importance of continued monitoring because as I pointed out, he did begin to develop some other symptoms as he got into his teens with the diminished mobility and also with the joint involvement, arthritis. We know these are manifestations of alpha-mannosidosis, so presumably transplant has not alleviated all of the clinical manifestations of the disorder, so I think it really underscores the importance of following the patient over time, even over the long period of time. His transplant complications have largely resolved, so from the transplant perspective he's doing fine and I don't think they are particularly concerned about him anymore or very involved, but I think continued monitoring for symptomatic intervention where needed is very important.
[00:21:36] Dr Karolina Stepien: Was there any challenge associated with this treatment-related monitoring?
[00:21:42] Prof. Barbara Burton: There are some challenges, yes. For example, we wanted before starting enzyme replacement therapy to try to get a six-minute walk test as a more objective measure of mobility and then to do it again after treatment, same with pulmonary functions. Unfortunately, the patient was not able to really do the testing due to the intellectual disability. He tried, but he just didn't really fully understand what was being asked of him, so we weren't successful in doing that. So I do think the intellectual disability can be challenging if you want to do some of the objective assessments that otherwise could be very helpful.
[00:22:26] Dr Karolina Stepien: Thank you so much, Barbara, and with this I hand over to Karolina for the next talk.
[00:22:37] Dr Karolina Stepien: Thank you, Christina. So I would like to talk about a multidisciplinary approach to care of our patients with alpha-mannosidosis. So multidisciplinary care is a treatment planning approach that involves a group of health professionals from different disciplines who work together to provide a patient with a comprehensive care. And these professionals work together to address as many aspects of patient's care as possible and the team composition may change over time as the patient's condition changes and with age different problems may become apparent. So the Delphi consensus included very important points regarding an integrated care coordination. Patients with alpha mmannosidosis should have a long- term multidisciplinary care team that includes an LSD specialist such as a geneticist or a metabolic specialist to coordinate team as well as a group of specialists with expertise in each patient's specific disease manifestation, including but not limited to audiologists, ENT surgeons, cardiologists, ophthalmologists, orthopaedic specialists, and it includes hip and knee and foot surgeons as well as a spinal surgeon, pediatrician, physiotherapist, occupational therapist, respiratory physician, social and family therapist, psychologist, radiologist, speech and language therapist, and many others.
Now, other specialties may also be consulted as needed for either emergency or a symptom- based care. And in rare diseases, obstetrics and gynaecology team may need to be involved during the preconception phase or to investigate subfertility or hormonal dysfunction management. And where possible, patients with alpha-mannosidosis should be seen in an MDT clinic, a multidisciplinary team clinic, to allow for coordination of care and reduction of the burden to the patient and their caregivers, their families. And when it's not possible, then a social worker or caseworker should be assigned to the family to aid in the navigation of care. So owing to earlier diagnosis and advances in treatment, the life expectancy of individuals with rare diseases in general has improved significantly. And over 90% of these patients will live beyond 20 years of age. And it's estimated that more than half of people with rare diseases are adults. So this shift towards an increasing population of adults with rare metabolic diseases, such as alpha-mannosidosis, has brought in a number of challenges, such as patients develop metabolic disease- related as well as age- related complications, such as cardiovascular diseases, diabetes, myelitis, or bone problems. We know that natural history of several inherited metabolic diseases in adulthood is not well described. In some cases, the metabolic progression may be accelerated. In other patients, it remains completely stable. Therefore, an appropriate transition from pediatric to adult services is key in optimizing care for individuals with alpha-mannosidosis. And the principles of the effective transition have been well defined. The role of a transition coordinator is key, and it encompasses more than just the administrative role.
We know that doctors in training should really have exposure to rare diseases to be able to look after adult patients with rare diseases later on in their life. Various protocols, various documentation should be standardized to enable the uniform way of managing these patients throughout a transition and adulthood. And we know that the planning of transition should start as early as adolescence. And I'll come back to that in a second. And we know that families, caregivers should be involved in the transition, should be actively involved to empower the children to enable the smooth transition and the transfer of care to the adult services. And we also know that a degree of flexibility is required to accommodate the individual patient's needs throughout the transition, meaning that some patients may require more visits in the transition clinic than others. Now, this is an example of transition strategy, which we previously developed with Christina and other colleagues. And it's very universal for lysosomal storage diseases, including alpha-mannosidosis. So the transition or visits in transition clinics start as early as 14, 15 years of age. But in other centers, it may start much earlier. We know that patients are asked to complete various questionnaires to evaluate their readiness to transition. But clinicians during these visits also assess patient's capacity and whether it changes over time. We know that the more complex cases, the more specialties, the more specialist teams are involved in their care. And ideally, patients should transition to other services, other relevant teams, neurology, orthopedic team, cardiology at the same time. We know that in some cases, the transition may be delayed if, for example, patients are awaiting a port, a port-a-cath replacement or awaiting a surgical procedure under the pediatric team's care. But it should not take place longer than when they are 18 years of age. Otherwise, they will not be admitted to the pediatric ward when they are older than 18. So I mentioned that there's a degree of flexibility required during the transition, and so patients, when they reach the age of 16, they are able to make their own decisions. They are able to consent for medical treatment, for even a phlebotomy or MRI scan and so on. But patients with intellectual disabilities, such as patients with alpha-mannosidosis may not have this poor responsibility for their own health. And this way I mentioned the assessment of capacity during the transition process and how important it is in the future care, because when they, when they transition to the adult services, a best interest meeting needs to take place to discuss pros and cons of various investigations, such as orthopedic surgery, such as MRI scan, anti-sedation, such as cardiac valve replacement and so on, and the clinicians, nurses, the patient, their caregivers are involved in these decisions to discuss the best possible option for this patient.
So now I would like to present a case of a lady who was diagnosed later in her life and the role of multidisciplinary team in diagnosing this patient as well as managing her during the surgical procedure. So initially, when she was born, she was a small child, 2. 6 kilograms at birth. There was meconium swallowing, but otherwise she was relatively healthy as a baby, then in childhood she required a hernia surgery around the age of three. Her mum mentioned that she struggled with speech in primary care and later she required a transition to a special needs school. She had problems with hearing and was diagnosed with accessory neural hearing loss and she had hearing aids fitted around the age of five. Her mum mentioned that she struggled with infections. She was easily acquiring infections, cold coughs, and she had adenoids removed. In childhood she had several ear infections and she required grommets. She had multiple episodes of tonsillitis. She had short stature- 148- throughout her childhood and then adolescence, and when seen by one of the pediatricians it was documented that she actually had mild prognathism, low set ears and mild cavies, but there was no evidence of peripheral neuropathy. So despite that, despite some health problems, she had a relatively normal quality of life and she was going to school in childhood until she developed some mobility problems and she was noted to have very unsteady gait, being prone to falls. It seems like it has progressed over time. She also struggled when turning, so it became more unsteady and had broad-based gait on turning. So in her 20s it became more pronounced and she started stumbling over things. She gradually developed ataxia and At the age of 27 she was referred to a neurogenetic clinic to investigate ataxia as given her very mild intellectual disability, hearing problems, she was thought or suspected to have a possible genetic condition and she remained under their care for a while just for monitoring of her symptoms. She became more unsteady and she was going to one side when walking she also developed hip problems and which further limited her mobility it became painful and she was referred to the orthopedic team for steroid injections initially to control the pain. But in the meantime the report of 100, 000 Genome Project came through and she was found to have two mutations causing alpha-mannosidosis.
So the first variant is a frameshift variant and is predicted to result in the loss of the protein function, and the second variant is a missing variant, and both are pathogenic variants confirming the diagnosis of alpha-mannosidosis. In terms of the biochemical workup her urine oligosaccharides confirmed tri-saccharide and ladder formation on chromatography. Her enzyme activity on the whole white cell enzymes analysis was very low, it was not deficient, but low at 2 nanomoles per mL per hour, and her chitotriosidase activity was non-specifically raised. So the pain and mobility issue were results of her left hip osteoarthritis with dysplasia of the left hip and genu valgum and her left knee. So the the left hip range of movements was grossly restricted due to due to pain and the patient had previous corrective surgery of both her feet with the full correction only on one side. So all this resulted in a limited physical activity and reduced her quality of life and the decision was made to operate on this patient but the MDT including hip surgeons, anesthetist, ENT surgeons, metabolic team and our specialist learning disability nurses have carefully conceded pros and cons of this procedure in this patients which we know was quite risky. So on the left-hand side, there's an X-ray of the left hip and pelvis, which showed subarticular cystic changes in the left femoral head and left acetabulum with a loss of joint space. The middle image confirms osteoarthritis with a complete obliteration of the joint space and synovial hypertrophy. So in summary she had severe osteoarthritis and background of hip dysplasia with large cyst in the acetabulum and while waiting for the surgery which was delayed due to several additional visits like ENT and airway assessments, a cardiology assessment and so on her pain was managed with opioids. So now 12 months after her surgery she is able to dance and walk and the swimming. She stopped her morphine, her opioids, analgetic agents and as a result her gastrointestinal dysfunction resumed so she reports a loss of stools and diarrhea more frequently. She has initially for a few months after the surgery suffered from iron deficiency anemia which seems to be under control at the moment. For many months after the surgery she reported cough which was believed to be caused by a complication of the intubation and and she developed endocrinopathy. So, apart from secondary amenorrhea, she also developed hyperparathyroidism. So she requires a review in the joint and the metabolic clinic at the moment. Thank you.
[00:39:58] Dr Christina Lampe: Thank you so much Karolina. I have one question, do you think this is a typical alpha-mannosidosis case?
[00:40:10] Dr Karolina Stepien: I would say it's not a typical for case. This patient has a relatively attenuated form of the condition. She had learning, mild learning difficulties and or intellectual disability and and she had hearing problems since childhood but this is what we see in our cohort of attenuated cases but all other problems such as mobility problems and joint problems, endocrinopathy and recently also she was found to have heart murmur, it all became more apparent in her late 20s and now 30s. So I would say she has definitely an attenuated form of her condition.
[00:40:58] Dr Christina Lampe: Which shows the wide heterogeneity of alpha-mannosidosis. Karolina, do you think there's a difference between the pediatric and adult service? You showed that the multidisciplinary team was in childhood and also in adolescence or in adult age was always present but is there any difference?
[00:41:25] Dr Karolina Stepien: As we usually say that the adult services are the mirror image to the pediatric services. There's a similar setup in terms of the adult specialist, specialist nurses, physiotherapists, we have infusion nurses and so on but we know that this is slightly different different focus. While patients under the pediatric team's care the focus is more on a child and the relationship is more between the clinician and and the parent. Whereas after the transfer to the adult services there's a slight shift to build the relationship between the young adult and and the clinical team. So patients may may have marked learning disability but we still ask them questions how they are and what the preference is and in the adult in the adult hospital. Plus we know that there are slightly different complications of the metabolic condition. We know that patients may develop cardiovascular problems like in our patients and endocrinopathies also develop heart valve murmur and so on. So there are complications related with the natural progression of the condition as well as age-related complication.
[00:42:57] Dr Christina Lampe: Thank you very much. I think we will have another panel discussion about the future of care in alpha-mannosidosis and Barbara how might the best practice Delphi consensus study recommendations be implemented in care?
[00:43:16] Prof. Barbara Burton: Well I personally think they're going to be very helpful in terms of guiding us in which types of assessments to do on the patients, what frequency to do those you know in terms of monitoring for complications. I think you know one comment I wanted to make with regard to the multidisciplinary care which I think is very important is that I think we have to recognize that the health care system varies considerably across different geographies and as I was listening to Carolina talk about multidisciplinary care and you know ideally the multidisciplinary clinic you know I'm thinking about our Center and also my colleagues in the U. S. and I think you know that is something that is often very difficult for us. So in our Center we certainly do use case managers, case coordinators to help coordinate the multidisciplinary care but we rarely are able to get all of the disciplines that need to see the patient together in one place at one time and I think that's just a function of how the health care system is structured. Also you know I'm envious of countries and centers where you have adult metabolic specialists because for the most part in the U. S. we don't and most of our geneticists and metabolic physicians follow the patient through the lifespan but we do of course have to engage adult specialists for the other components of the multidisciplinary care. So we don't let go of the patients. I'm trained as pediatrician initially. We don't let go of the patients when they become adults. We continue to coordinate their care and take care of them. But we do have to make that change from pediatric specialists- ENT, pulmonary etc- to adults and unfortunately many of our adult specialists are not as familiar with rare genetic disease as the pediatric specialists. So I'm envious, where we do have that, of centers who do have that. But certainly some transition process is very important for us as well. You know, if the patient is able to take more responsibility for their own care. Of course, making that transition from parent coordinated care to the patient taking additional responsibility, you know, is very key and also guiding the patient in those other transitions.
[00:46:09] Dr Christina Lampe: Yeah, Barbara, we have the same in Germany. It's very difficult to have adult clinics who are taking care of our patients, the metabolic ones- so we have only two centers who have this possibility, but we others we are taking care of our patients the whole life. So any comment from you, Karolina, before we we enter the question and answer session?
[00:46:43] Dr Karolina Stepien: Just to say that ideally, like Barbara said, all the specialties involved in the patient's care should be under the same roof in the same hospital, but we know it's not always the case. Plus, the patients often live away from the tertiary center, so they need to have clinicians involved in the care, clinicians locally if, in terms of follow-up, sometimes patients are unworthy, are not able to travel to the specialist center. So we very much rely on their support in terms of repeated investigations, repeated phlebotomy, so it's a kind of a shared care model, but we obviously guide them and and we can pass on any correspondence, any instructions to them how to follow them up.
[00:47:37] Dr Christina Lampe: Great, thank you. So please submit your questions to the chat box so that we can discuss your questions, and I just want to give you the information that each webinar in this series has some infographics that are available on the on-demand videos as well. So let's see the questions. The first question is: as lifespan improves, how can we prepare for the needs of aging patients? Karolina, you want to start, since you are seeing most of the adult patients.
[00:48:27] Dr Karolina Stepien: So, yeah, I think. Well, I mentioned the principles of transition, right? So we know that both the pediatric and adult teams are involved in in the transition process and it's not just one clinic, it's several clinics, and the more complex case, the more clinic visits are required, but it requires training. It requires a training of doctors, nurses, the whole teams and and and we know that it's not always possible to have the transition clinic like Barbara mentioned. But we need to make sure that the adult clinicians who may be involved in this patient's care in the future- such as adult neurologist- there may be obs and gynae doctor- there may be adult endocrinologist- they they need to be aware of the condition and what complications they may encounter in these patients in the clinics. So we need better training. We need robust guidelines, protocols and webinars like like this to educate our colleagues.
[00:49:40] Dr Christina Lampe: You want to add, Barbara?
[00:49:43] Prof. Barbara Burton: No, I agree with that completely. I'm hopeful as we get more and more patients surviving into adult life, not just with this disease but with other rare genetic metabolic disorders, we will have an increasing level of interest among the adult specialists in this as they have the opportunity to see more and more patients. But I think for now, you know, it's incumbent on us to try to identify individuals, you know, in the adult provider groups who are interested and willing to learn, even if we don't have someone who is really expert in the condition because there may not be people like that. They just haven't had enough opportunity to see them. But if we find colleagues who are willing to learn, I think we can provide them with literature and education and, you know, help to identify people who can assume that role and then gradually as they see more and more patients, of course, they develop additional expertise.
[00:50:47] Dr Christina Lampe: There's one question I think, Karolina, maybe you can answer. How early should we begin planning for the transition to adult care? At what age stage? 14, 15 years? Any earlier?
[00:51:06] Dr Karolina Stepien: It probably depends on the capacity because we know that more and more young adults transition to adult clinics and we have monthly transition clinics at the moment. But we cannot accommodate all adolescent patients in this clinic. So those who are relatively stable, they may start attending the clinic at the age of 15, 16. But those who are more complex, they need to attend adolescence clinics and then transition clinics from the age of 13, 14. And the family as well as the patients need to be prepared for the transfer of care. As I mentioned, that obviously patients like patients with alpha-mannosidosis, they remain under several other teams. And the transition should occur around the same time to the adult services. So adult neurologist, adult orthopedic, adult cardiologist and adult metabolic. So the sooner it starts, the better. It helps the family and the young adults to engage more with the adult services. And then, hopefully, after the transfer of care occurs, they will engage more with the adult services.
[00:52:27] Dr Christina Lampe: Barbara, when do you start your transition, even if they stay with you? But in a way, there's a transition.
[00:52:37] Prof. Barbara Burton: Yeah, absolutely. I think I agree with arolina that to some extent it depends on the patients and the capability of the patient. If we have a patient who has the intellectual capability, we certainly with the patient start trying to do that transition to more autonomous care by certainly 14, 15 years of age, starting to spend some time with the patient alone, sometime with the family in the room as well, providing genetic counseling and education to the patient about their disease. I think oftentimes we forget that we've done very extensive education about the disease and how it's inherited and all of that with the family when we have a young diagnosed patient, but that doesn't transfer into the patient by osmosis. You know, so we need to again re-educate the patient. What is it, their disease? You know, what is the purpose of their visits? How is it transmitted? They may know it's genetic, but not have any concept of whether their kids would have it or not, and so all of that we start discussing with the patients. Now, if you have a patient who has more severe intellectual disability, you know, obviously that may not be possible, and then we start talking with the family about what the plan would be, for transitioning to other providers, and at our center, you know, most of our patients can continue to get care from pediatric specialists, certainly up to 18, in some cases up to 21, sometimes 25. Our pediatric specialists have different policies and preferences with regard to how long they follow their patients, and so we figure out what we need to do in each case and, you know, help the patient with that along the way.
[00:54:40] Dr Christina Lampe: Yeah. Do you both think that digital health technologies, for example, telemedicine, wearable devices, could change the monitoring of our patients, and do you use them?
[00:54:58] Dr Karolina Stepien: I will start on answering this question. So we have years of using telemedicine in our clinical practice. We cover a large population of around 10 million in the north of England and northwest and it's not always possible to follow patients up every six, every 12 months face-to-face. Patients have disabilities, they have transport issues or just simply cannot afford travelling so frequently. But as long as we see them with our MDT once and they have a full set of investigations, so subsequent follow-up may happen via telemedicine or we may see them once a year in our centre, as it's a requirement, in particular for conditions where we prescribe treatment. But in the meantime we can follow them up via a telemedicine similar.
[00:56:01] Prof. Barbara Burton: Really we use telemedicine. We learned to use it during COVID. We weren't really in the process, you know, we had not established it at our centre prior to that time, but since then we have learned that it's very helpful for many patients who, as you say, may live a long way from the centre. So we do use it. We wouldn't use it for an initial assessment of a patient, but definitely for follow-up assessments it can be very helpful.
[00:56:37] Dr Christina Lampe: There's a question concerning treatment planning. Which healthcare providers often have the biggest impact on the quality of life of patients. Do you want to start, Barbara?
[00:56:53] Prof. Barbara Burton: I would just say you know that's going to depend on the individual patient. I mean, I'm thinking back about the case Karolina presented and it sounds like perhaps the orthopedic surgeon had the biggest impact on her life in terms of the pain and, you know, related to her hips and orthopedic issues. But that wouldn't necessarily always be the case. You know, another patient may have more significant issues in another area. I like to think that, as you know- metabolic physicians, geneticists- we have the biggest impact because we're making sure that they get to all of the proper specialists that they need to see, regardless of what their issues are, and we're identifying those issues. So I think you know there isn't one. We can't say that one specialist you know really fills that bill. I think everyone involved plays a really important role.
[00:57:52] Dr Christina Lampe: Thank you very much. Actually, we are almost at the end of this webinar and I thank you, Barbara and Carolina, for this discussion. My voice is not good enough to discuss with you, so I think we will come to an end of this webinar. I think it shows the heterogeneity of the disease and it showed also the wide multidisciplinary, the need of a multidisciplinary team for our patients, independent of the severity of the disease. But not only the medical follow- up is important, but also the social and psychological resources that should be available for our patients. And I hope that I could see the next slide now, because we would really like you to answer our questions, if you like this webinar, and make a suggestion what we can improve and what we can do better, and I thank EIP for this organization of the webinar and Chiesi. I thank you, Karolina and Barbara, and I think we say goodbye here. It's evening. Barbara, I think you are in the morning, so goodbye and take care, thank you.
[00:59:31] Prof. Barbara Burton: Thank you so much, everyone. Have a good day.