Understanding the Mucopolysaccharidosis (MPS) Patient and Family's Needs (MPS-S5-M6)
00:32:08
Transcription
[00:00:00] Dr. Christina Lampe: Hello, good evening and good afternoon to our fifth webinar today. It's a series of a lot of webinars about mucopolysaccharidosis. This will be the last one. And the title of the whole series was Avoiding the Misdiagnosis and Delays in Diagnosis of MPS Children. And my part will be the better understanding the mucopolysaccharidosis patients and families' needs. Some housekeeping notes, please do not take screenshots or reproduce the slides. And there will be a chat at the end. So whenever you have any questions, please fill in the chat and we will discuss after the talk. And the recorded webinar will also be online available. You see the link here so that you can also hear it again if you want. So better understanding the MPS patient and family's needs. There are my disclosures. And the outline will be how a pediatrician can best support MPS patients and their families. I will make a short summary of the last talks you heard. What do a pediatrician need to pay attention to in particular with MPS patients and the importance of communication between the centers, professionals, families in managing MPS patients. So actually, we are talking not only about one disease, we are talking about very rare multisystemic genetic and chronic progressive life-threatening diseases. So it's a group of diseases which have a high variability and heterogeneity in symptoms and organ involvement, 70% have CNS involvement. And as I said, MPS is not only one disease, there are seven types and 11 enzyme deficiencies leading to MPS. We see it here, it's a huge group of very similar, but in some cases or in some aspects also different diseases. We see that heparansophate, which is here marked always in red, is leading to a CNS involvement. So we have MPS4 and MPS6, for example, that never have any CNS involvement. But we can have it in MPS1, in MPS2, and MPS7, and in MPS3, the main disease complication is the CNS involvement. So if we see the clinical overview of the MPSs, we see we have one group, the hypermobile ones, so MPS4A and B, two diseases that look very similar clinically and have more hypermobile joints. We have a bigger group of MPSs, so-called the stiff ones, MPS1, 2, 6, and 7, that look clinically very, very similar, but the enzyme deficiency is different. And we have the MPS3, as I said, more a disease of the CNS. Very similar to this group of diseases is the alpha-manocidosis, and we will have some more webinars in the next time about this disease, which was also called Hurler-like syndrome because it is very similar to MPS1, the severe one. The spectrum of the disease severity and the progression is very wide. This is what you heard already in the last webinars, the variability of signs and symptoms, the wide spectrum of disease severity, the disease severity in specific organs may differ in the same patient. We have slow and late onset. We have a coarse phase that can be very, very mild in some patients. We have patients with and without cognitive involvement. We have normal but also behavioral difficulties, so the diagnosis might be extremely challenging in MPSs. Additionally, we have also a multisystemic disease, as I said at the beginning, which is chronic progressive, but nevertheless, almost all organs are involved in the disease. So these patients need, for the best or optimal care, a multidisciplinary team and also some physicians that are really specialized on MPS or know MPS. So it is always necessary for MPS patients to be connected to a specialized center. The diagnosis is, in all senses, a challenge. It is a rare disease, so there's quite a lot of lack of awareness for these diseases. There's no single or specific MPS symptoms. So the first signs and symptoms like infections of the airways or ears, hearing loss, macrocephaly, inguinal hernia is very common in childhood, and it's mimicking common diseases of childhood. So it is very unspecific and for this reason very difficult to diagnose these patients, also for specialists, by the way. So only the combination of these unspecific symptoms is leading to a diagnosis, and as always, you only see what you know. The delay in diagnostics for all MPS types is shown here, and the mean delay time to diagnosis is around three years. In 20% of cases, more than 10 years, and actually 40% in this survey did not know the link between the certain symptoms and MPS. And you see the delay in diagnosis is still very common, although we have the enzyme replacement therapy since several years. And we see here in MPS four, it is six and a half years, in MPS three, six years. So it's quite a long time to diagnose these patients. The situation for a patient which is not diagnosed is very heavy. Most of the parents are not taken seriously, especially if the patients have more mild or attenuated phenotype. They have an odyssey from one physician to the others. They search for experts that they don't find because they don't know where to link to. They have an uncertainty what is going on, if this disease is inherited or not. They have sometimes problems with authorities or insurances for rehab for artosis and so on. So it's actually a very difficult situation not having a diagnosis for each rare disease patient. Misdiagnosis are quite often, especially because the MPSs are very similar to skeletal dysplasias. And for most skeletal dysplasias, there's no treatment available. So people think it is a dysplasia and they send the patient away. Also wrong treatment is very common without proper diagnosis, meaning surgeries that are not necessary or not useful for MPS patients. The delayed diagnosis means for sure a delayed treatment. And especially in the chronic progressive diseases, it is extremely important to start as early as possible to avoid irreversible organ damage. To have a diagnosis means to check the therapeutic options. It can lead to participating in clinical trials. It helps to connect to a center of expertise. Family planning is a big topic that can be discussed. And it is also possible to connect to a patient association. For the therapy, it is important to have a multidisciplinary treatment for these patients. First, to detect the life-threatening disease complications, but also to detect the quality of life-limiting disease complications in these patients. So no diagnosis means also no treatment or even worse, the wrong treatment. Clinical management and optimal care. We spoke a lot about medical care of these patients, which is for sure most important, especially as a physician. But to take care in an optimal way in MPS or in chronic progressive diseases, it's also the psychological care, the medical legal and the social care that is needed for this patient. So there must be involved also social workers, health insurances, authorities, teachers, nurses, psychologists, lawyers, et cetera. And this is also even more important for patients with the CNS involvement. Patients with the CNS involvement are affecting the whole family. And any illness of a child, especially a severe or incurable one, is an event that causes a wide range of psychological effects, not only for the affected child, but also for the whole family, the physicians, the siblings, the friends, the teachers, and so on. So it is a disease of the whole family. And if we see here how parents describe their feelings having a child with an MPS, they feel upset, confused, frustrated, devastated, and they feel guilt. They feel their life is a roller coaster. They are left waiting, waiting, and waiting. It's like watching a time bomb because the progression of the disease is in waves and not straightforward. And patients wish or they want him to be educated, independent, working, house, family, just happy, doing the normal run of the mill things. I wouldn't want to see him in a home or institution. Also, parents who have a child with MPS display a stronger tendency to suppress experienced feelings of depression. They are more vulnerable and have emotional difficulties. These parents have often an increased risk of developing chronic illnesses themselves. And the psychological condition of parents influence the emotions experienced by the children and the course of their further development. So it is extremely important also to take care of the whole family. And also the parents are very concerned that their unaffected child might be ignored or to be jealous of the affected child. So the parents and the whole family are suffering. For sure, there are not many physicians that are experienced with MPS, so it is difficult to find an expert for their children. It changes or to have a diagnosis like MPS changes the whole family life including vacation, fewer friends, no time for social activities, difficulties obtaining child care especially with the behavioral problems in some MPS types and also embarrassment when going out if the child is hyperactive running around and they have no time alone anymore. So for the family and the friends it is actually a quite difficult situation especially because the children's sleep patterns are unpredictable so that means they're awake during night and sleep over the day so it is very difficult to plan activities and they have to be much more flexible in responding also to the child's needs. They have a higher cost for care, medication, food, etc. and it's the time consuming daily care for the children. And I would like to show you one video of an MPS2 mother, so Morbus Hunter's disease. She explains the situation. The video is in German but it is translated so that you can read what she says and how she feels.
[00:14:07] Dr. Christina Lampe: Okay, the next video is from an adult patient that I will skip now. But to show how the situation in Europe is about the psychological support and this was a survey monkey tool, 77 centers of excellence for metabolic diseases and 65 centers answered. And what you can see is for a patient, the availability for psychological support is around 36% but the need is more than 66%. For the parent or caregivers, the availability for psychological support is less than 30% and the need more than 70%. So actually this is a situation that is making the life with MPS much more complicated. In the medical management, going back to the physician stuff, you see that in blue, these are all the organs that need any surgical intervention, so inguinal umbilical hernia, the otitis, adenoidectomy, tonsillectomy, T- tubes, etc. Heart valve involvement and heart valve replacement is quite common. The carpal tunnel syndrome need to be decompressed. Hydrocephaly needs to be shunned. Spinal... decompressed. But also in the skeleton, we have the hip dysplasia that needs sometimes but not always some surgical intervention. We have the kyphosis and scoliosis but much more common in the skeleton are the knock knees that need some surgical correction. So what we see is that MPS patients need several surgeries and, for sure, additionally symptomatic treatment. The problem in MPS is that they have a high anesthesia risk and it's quite a challenge to operate an MPS patient. First, it's the difficult positioning due to the deformity of the chest cage, the enlarged abdomen and the contractures. And one of my MPS two patients was diagnosed because of the contractures when they wanted to position him in the surgical theater for an ENT surgery. They have difficult airways. They are short. So also this is something very, very important to know that the airways are even in adult patients with the short stature, they need a pediatric intubation tube, etc. They have a short neck. They have a large head. They have thickened and less flexible airways and epiglottis. They have narrowed airways and macroglossia and also the cervical spine flexibility that is difficult in the atlanto- axial instability. So there are quite a lot of things to know before operating an MPS patient. There's also the limited deo- respiratory resources of that patient and the limited cooperation in patients with intellectual involvement. And post- operative, these patients need intensive care, also a weaning and we have to avoid airways swelling. So the higher perioperative mortality is known in MPS. So we need specialized centers to take care of the patients. Due to this greater surgical risk, specific actions are required prior to anesthesia and surgery. So for example, the anesthetist should be experienced in treating MPSs to supervise the pre, peri, and post- operative care. The access to intensive care unit should be available in the moment when you operate an MPS patient. In surgeries, it might be considered with extreme caution to avoid general anesthesia in a high- risk situation or during pregnancy. ENT, respiratory, cardiac, and radiological assessments require prior anesthesia. And I will show you in the next slide what you have to check before. You have to maintain a neutral neck position, especially in patients with an atlanto- axial instability. And you have to be sure that you have the intubation stuff ready for the narrowed airways. You see here the medical management or check- up of all potentially affected organ systems in these patients. So first, the life- threatening disease complications like the CNS, the respiratory, and the cardiac. So you need quite a lot of assessments from time to time, especially also prior anesthesia. And the quality of life- reducing disease complications like the skeleton, the eyes, the ears. So at the end, it is a real holistic approach that you have to perform an MPS patient. And you have to be always aware of the anesthesia risks. The next step whenever you have diagnosed a patient, you have to think about the treatment options. For the diagnosis in some countries, newborn screening is available, unfortunately not in Germany, but this would be the first step to diagnose early. The second is what kind of therapy is available. Is it a stem cell transplantation in a severe affected MPS1 patient under the age of two years? Is it enzyme replacement therapy that is available? Or is there only palliative care available? Or are there any clinical trials that you can find for the patient like the gene therapy ex vivo or on vivo, substrate reduction therapy, modified ERTs that are crossing the blood- brain barrier? At the end, it is always symptomatic and any standard treatment that is available and necessary for the patient. The importance for early diagnosis and long- term treatment is here summarized. So the diagnosis as soon as possible is optimizing the patient's outcome. The management in a multidisciplinary team, the baseline, meaning making all the assessments before starting any treatment in order to see the progression of the disease with the treatment. And also if available as soon as possible, the treatment with enzyme replacement therapy after the diagnosis is confirmed. To give you an example of disease complications and comorbidities, here's an MPS2 patient or a Hunter's patient that was diagnosed at the age of four years. Although the first symptoms appeared at the age of four months, this is a case where the anesthetist in the operating theater or recognized the contractures of shoulders and was thinking to a lysosomal disease. This patient was actually treated symptomatically from time to time whenever any complication appeared up to the age of 12 years, but not in a standardized way, not every six or 12 months in order to avoid any disease complications, but just from time to time. He underwent several surgeries like ENT, hernia repair, hemiepifusiodesis of the knees, which were all quite useful and good for the patient, but also a lengthening of the acral tendons, which was absolutely unnecessary and not helpful for the patient. But nobody knew about the disease. It was not a specialist who was taking care of him. Although the enzyme replacement therapy was available in 2007, the patient didn't know about because he was not linked to an expert center. He was not linked to the patient association. But when he heard by chance via that about the enzyme replacement therapy, he went to a specialized center in 2011. He started the enzyme replacement therapy. He received regular follow- up assessments and symptomatic treatments. So if you see this patient at the age of 12 years and you see here all the specialists the patient has visited in his time, for sure the pediatrician and then the metabolic specialists, but also the orthopedics, the neuroradiologists, the physiotherapists, the dentist, the dietician, the neurologist, pulmologist. So really a big multidisciplinary team around this patient. So management of MPS patients, what is the role of the general pediatrician or the pediatrician near home? For sure the patient needs a multidisciplinary team approach due to the multisystemic disease. All organs need to be checked in order to prevent irreversible organ damage, meaning prevention is a very, very big topic in MPS patients. But at the end, the pediatrician sends the patient to the specialized centers, but he should get feedback from the centers afterwards because he's close by the patient's home. The centers are most of the time very far away from the patient's home and they have to drive several hours to see the specialist. So at the end, the pediatrician is in charge whenever there's an urgent problem. So actually the best way of treatment would be that the pediatrician is taking care of the patient close by home for all the urgent or the emergencies of the patient in cooperation with the metabolic specialist with planning and organizing the necessary assessments in a multidisciplinary team, also discussing the results in the multidisciplinary team, meaning if a surgery is necessary, the orthopedic says it is a necessary surgery. The anesthesiologist says we have a high anesthesia risk. The cardiologist says from my side, it is fine. So it's a discussion to make it as safe as possible for the patient to get any surgery. At the end, for sure, we have to discuss our results with the patient or the family, and then also to give feedback to the pediatrician in order to keep him so updated that he exactly knows what is going on, how the multidisciplinary team and the metabolic specialists made their decision and to have the best care close by home for the patient. So only the collaboration leads to an optimal care at the end. So to summarize my talk, which was more a summary of all the four other webinars you heard by now, to find a diagnosis early is the most important thing in chronic progressive diseases, for sure. These MPS patients have a multisystemic involvement and they need specialists who are taking care of them. This means the patient need to connect to a specialized center for the baseline before treatment, and then also the treatment options and the regular follow- up and the symptomatic treatment. They have a high anesthesia risk that need really a specialized team that the patient can receive all the surgeries in a very safe way. However, all these patients and families need their home pediatrician or the pediatrician that knows the child since the child was born. He needs to take care of the patient because he knows the patient best at the end. And very important is, and this is what I wanted to highlight today, is also to pay attention to the psychosocial burden of the whole family. So also the connection to the patient association is extremely helpful for the parents and patients in order to exchange experience, to get new information about new trial studies, about new symptomatic treatments, and also recommendations how in the day, daily life, how to manage sleep problems. problems with behavior, etc. So optimal care is not only medical care, but it is also psychosocial care. And the collaboration between pediatrician and specialized center is essential for an optimal care of the family and their patients. And with this, I thank you for your attention and this series of webinars. I thank the EIP for organizing that. And I'm very happy to receive your questions now. Thank you for listening. Here's one question. At what point should I raise sibling testing at the point of first child suspicion symptoms or a diagnosis? This is a difficult question. I think whenever you have high suspicion of a disease, I would also test the sibling. But nowadays with the dry blood spot tests, you'll receive the result of the testing after two to three weeks. So you can also test one sibling because sometimes, as I said at the beginning, especially the patients with the stiff joints, it is very difficult to decide whether it is an MPS 1, 2, 6 or 7, it is better to wait and then to test the sibling afterwards. The next question is, you mentioned looking out for the parents' mental health. How can we support them in practice when the child is often our main focus? What practical advice to offer? Well, I mean, also in Germany, it's a very difficult situation to find psychologists that are taking care of patients, but also the parents. What I always try to do is to involve the family as much as possible so that they really feel inside of the treatment plan or the child's medical care. What I also try to do is to recommend psychological support because this is, in my opinion, one of the most important facts or things for the families. But also the MPS Association has very good psychologists for advice to support. And also this will help the parents and families quite a lot to manage the situation. What are the most common communication problems that you find when working across specialties on complex MPS cases? What to look out for? Actually, I'm a surgeon by training, so I know what I'm talking about. The most difficult discussion is for sure with surgeons because surgeons have usually no idea from any metabolic diseases and metabolic complications. So most important is actually, or this is the most difficult, that the surgeon says this surgery is necessary, but the others like anesthesiologists, pulmonologists, cardiologists tell that the anesthesia risk is too high. So actually this is the most difficult. And for this, it is so important to have this multidisciplinary team discussions. So not only as a metabolic specialist collecting all the data or the information and make a recommendation, but really to discuss the cases inside of the multidisciplinary team. No further questions, I see. So at this time, if someone has another question, now it's still time to ask. Okay, then I thank the audience. Thank you for participating this last webinar of this series. As I said, there will be very, very interesting ones in the near future. So thank you very much for listening and think that whenever you want, there will be a streaming as well whenever you want to forward to a colleague or you want to watch the seminar again. Thank you very much.