Home About Idorsia Our responsibilities Investors Media Careers Contact Idorsia today Idorsia people Target diseases Partnerships Are you looking for more information about Fabry disease? + About this eBook Introduction “The sensations that I get – it feels like my hands are on fire. It feels like there’s a thousand needles poking at my hands and feet… If I was to get out of bed and I was to walk, it would feel like I’m walking on hot coals with needles jabbing into my feet.” - Patient Fabry disease is a rare inherited disorder in which a particular lipid (a fat-like substance) can’t be broken down by the body, leading to its build-up in the cells of the body organs. Fabry disease is often undetected or misdiagnosed. Its symptoms are non-specific, and many people are not aware of the disease. Early symptoms such as pain in the hands and feet, rashes on the skin, and digestive problems, as well as more advanced symptoms such as kidney disease, heart disease or stroke could be caused by any number of diseases, which will usually have to be ruled out first. People with Fabry disease have a lower life expectancy than the general population. Fabry disease is progressive, which means that as the build-up of lipids in different organs of the body continues over time, its symptoms become worse. Therefore, early diagnosis is important to manage the symptoms as soon as possible and to reduce the risk of developing serious complications. Early diagnosis also makes it easier to identify other family members who may be affected by the disease. Understanding Fabry disease “I don’t have pain episodes like my children do. I have several children who have Fabry also, and the boys – three of my boys – have severe pain episodes.” - Patient What is Fabry disease and what causes it? Fabry disease is one of nearly 50 so-called lysosomal storage disorders. These disorders affect a part of the cell known as the lysosome, which, among other things, is responsible for breaking down lipids. If the function of the lysosome is impaired, the lipids can’t be processed properly, resulting in their accumulation in different parts of the body and in subsequent damage to cells and organs. Fabry disease is caused by a mutation in the GLA gene, located on the X-chromosome. This gene is responsible for the production of a specific enzyme, alpha-galactosidase A (α-GalA), that is mainly involved in the breakdown of the lipid globotriaosylceramide (Gb3) in the lysosome. In people with Fabry disease, the enzyme is deficient, so Gb3 can’t be broken down and builds up in the cell. Over time, this may result in deposits throughout the body, particularly in the kidneys, heart and nervous system, leading to a variety of symptoms. They range from pain in the hands and feet to kidney failure, heart disease and stroke, depending on how much the organs of the body are affected. + What is the role of lipids in the body? + Types of Fabry disease Progressive damage to vital organs occurs over several decades. It results in end-stage kidney disease and/or life-threatening complications that affect the blood supply to heart or brain, causing substantial morbidity, significantly impaired quality of life, and premature death. How is Fabry disease inherited? The defective ‘Fabry’ gene is located on the X-chromosome, of which men have one copy and women have two. Both men and women with the defective gene will have Fabry disease in some form, but men are typically more severely affected, and women potentially less so, and more variably. This variable expression of Fabry disease in women is thought to be influenced by the inactivation of one of the two copies of the X-chromosome. Because of the typically milder or absent symptoms, there was the assumption that some women could be ‘carriers’ only and not have the disease themselves. Today, it is emphasized that all women who have an increased risk seek testing and potential treatment to slow the build-up of Gb3, even if they have no apparent symptoms. + Fabry disease inheritance pattern + What is the role of genetic testing? How common is Fabry disease and who gets it? Fabry disease is a rare condition that can affect people regardless of their ethnic background. Prevalence (i.e. the proportion of a population who have or had a condition in a given time period) for Fabry disease is estimated to range from 0.27 to 1.69 per 100,000 in men, and 0.33 to 3.47 per 100,000 in women. Signs and symptoms of Fabry disease The symptoms of Fabry disease are non-specific and often resemble those of other diseases, leading to frequent misdiagnosis. A variety of symptoms can appear at different stages of the disease, or some symptoms not at all, depending in which organs the fat deposits build. + Parts of the body affected by Fabry disease + Early onset symptoms + Later onset symptoms + Life expectancy + Neuropathic pain Diagnosis and treatment of Fabry disease “In high school, I remember having some episodes where I was just in so much pain, I just didn’t get it. There was nothing wrong with me that anybody could see, but I just felt the swelling in my hands, the burning pain, the itchiness… I didn’t know what to do about it” - Patient There are two typical routes leading to a diagnosis of Fabry disease: either the patient is the first person to be diagnosed in his/her family, or he/she has been tested because another family member has already been diagnosed. While the diagnosis of a second family member is usually relatively fast and straightforward, as Fabry disease is already suspected and simple biological tests can prove or disprove the diagnosis, reaching a diagnosis for the first family member can be much more arduous. Due to the low awareness of this rare disease and the non-specific nature of the symptoms that can be mistaken for other conditions, it often takes years of frustration and deteriorating health before a patient is referred to a specialist who can successfully diagnose Fabry disease. + How is Fabry disease diagnosed? + Family history and prenatal diagnosis What treatments are available for Fabry disease? There is no cure for Fabry disease; however, treatment is available to slow its progression and manage its symptoms. Early diagnosis is vital, so that patients and their families can access support as soon as possible and begin treatment to maintain the best quality of life possible and reduce the risk of more serious complications such as kidney or heart failure, or stroke. Different medicines are used either to relieve the individual symptoms of Fabry disease or to specifically treat the disease itself. For the latter, two different approaches are available that reduce the build-up of Gb3: Enzyme replacement therapy (ERT) is aiming at replacing the defective enzyme in the cells of people with Fabry disease, regardless of their mutation. Chaperone therapy is aiming at enhancing the residual enzymatic activity in cells in a sub-group of people with Fabry disease. Ongoing studies to investigate the effect of different treatment modalities on the biological processes involved in Fabry disease may lead to the introduction of new medicines in the future. + How does Fabry disease progress over time? + Enzyme replacement therapy + Chaperone therapy + Symptom management + Which healthcare professionals are involved in the treatment of Fabry disease Burden of Fabry disease “I’m a delivery driver. Sometimes the numbness in my hands makes delivering cases more difficult… I can still lift the cases and things like that, but small movements with my hands… sometimes it’s hard for me to control them.” - Patient Physical symptoms such as pain and fatigue can have a serious impact on the day-to-day activities of someone living with Fabry disease. The emotional and social impact of the disease can be just as life-changing. It is important to remember that the person with Fabry disease is not the only person affected, but their family and friends may also struggle with the uncertainty and changes brought on by life impacted by the disease. Fabry disease can impact a person’s ability to work either full time or at all, given the unpredictability of the symptoms, the long-term effects of more serious complications such as stroke, and the management of cumbersome therapy and frequent medical appointments. If someone is not working, or if a parent needs to take time off if their child is unwell, this can have a financial impact on the individual and the wider family. + Coming to terms with the diagnosis It is worth talking to employers about the condition, as it may be possible to adapt responsibilities to work around symptoms and treatment. Social workers and patient associations should be able to advise on financial benefits available to families affected by Fabry disease in their country. Impact on children Fabry disease can impact a child or young adult’s education, with time off needed for regular hospital appointments or due to illness. Physical activities such as sports at school can be more difficult for children with Fabry disease to take part in because of the pain and tiredness caused by the disease. As a result, children and young adults with Fabry disease can become isolated from their peers, being seen as less able to ‘keep up’ with their friends or excluded for being ‘different’. It can be helpful for parents or young adults to meeting with the school or university ahead of the academic year to discuss any practical needs in advance, such as timetabling around hospital appointments, addressing physical education classes and how to explain the condition to other students. “In school, I remember having some episodes where I was just in so much pain, I just didn’t get it. There was nothing wrong with me that anybody could see, but I just felt the swelling in my hands, the burning pain, the itchiness… I didn’t know what to do about it – what would help.” - Patient Practical guidance on managing Fabry disease “You try to stay positive... but it’s very emotional and it drains you.” - Patient There are a number of things that people affected by Fabry disease can do to help themselves manage the condition more effectively and feel more positive about living with the disease. It is natural to feel overwhelmed sometimes. Friends and family can be unsure how to help, so it is best to be honest about what is needed to allow them to give appropriate support. An individual’s diagnosis may also lead to diagnosis in several members of the same family, so it is important that everyone has access to genetic testing and counselling. Learning as much about the disease as possible can help people affected by Fabry disease to feel more in control and make more informed decisions about their health. However, the vast amount of literature and information online can be overwhelming and even contradicting sometimes, so it is important that people read it at a pace that is comfortable for them, when they are ready to absorb it. Knowing where to look for reliable and digestible information such as booklets, videos and news updates from patient organizations can help with this. Keeping notes of any questions to discuss with healthcare professionals at the next appointment can also be useful. + Managing pain + Managing fatigue Reaching out for support Some people find support group meetings or online forums very valuable, allowing them to speak with and learn from other people who are going through similar experiences. The level of support for families affected by Fabry disease varies greatly from country to country. Local associations and healthcare professionals can often be a good source of information about benefits, grants, social services and other resources available. In addition to care from a specialist, people with Fabry disease may also benefit from being referred to other multidisciplinary team members, including psychologists, to offer emotional counsel. It is normal to feel shock and grief after being diagnosed with a progressive, life-long disease, but it is important to know that people with Fabry disease can still lead rewarding, happy lives. While there may be things that are more difficult to do or achieve with Fabry disease, setting realistic goals and focusing on what is still possible can make it easier to maintain a positive outlook. Talking to other families affected by Fabry disease can often be helpful for coming up with ways of adjusting to a new reality and coping with the challenges that the disease may present. There are many patient associations dedicated to supporting patients and their families to live well with Fabry disease by providing detailed information and practical advice. A list of organizations around the world can be found on the Fabry International Network website at www.fabrynetwork.org/members + Disclaimer Introduction Understanding Fabry disease Diagnosis and treatment of Fabry disease Burden of Fabry disease Practical guidance on managing Fabry disease FOLLOW US: VIEWING OPTIONS This website is subject to the terms and conditions outlined in the legal and privacy statement. Last update: 23.03.2021 Legal & privacy statement|Site map|Cookie policy|Webmaster Copyright © 2021 Idorsia Pharmaceuticals Ltd