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Living with Fabry Disease A guide for patients, parents, relatives, and friends Supported by Supported by The information in this booklet is not meant to take the place of professional medical advice. Always consult with your healthcare provider if you have questions and/or concerns about your medical condition. Understanding Fabry Disease: from diagnosis to action Fabry disease is a rare inherited disease that shows up in different ways.If you or someone you know has been diagnosed with Fabry disease, it can be difficult to imagine how this disease will affect your health or the health of those you care for. And because the disease is rare, it is not easy to know where to turn for information, guidance, and support. We hope that gaining a better understanding of Fabry disease through this booklet will help you as you begin to move from diagnosis to action. How this booklet can help you Treatment is available. This booklet provides information about Fabry disease and how it is diagnosed and managed. It also offers practical tips on living with Fabry disease. As you read through the booklet, keep in mind: Over the last several years, a great deal has been learned about Fabry disease through the collective efforts of healthcare professionals, scientific experts, and patients worldwide. Enzyme replacement therapy to treat the underlying cause of Fabrydisease has been approved for use in several countries around the world. Although ERT is not a cure, it can slow or halt the progression of Fabry disease. You are not alone. There are active patient groups and caring health professionals throughout the world who can help you manage the challenges of living with Fabry disease. Being informed can help you take a more active role in your care. Learning about Fabry disease and disease management can help you work with your healthcare team to get the best possible care. What’s Inside: What is Fabry disease? What are the symptoms of Fabry disease? How is Fabry disease diagnosed? How is Fabry disease managed? What can I do to make it easier to live with Fabry disease? What is Fabry disease? Fabry disease : A lysosomal storage disorder Fabry disease is an inherited disorder. It is one of a family of hereditary diseases called lysosomal storage disorders that affect the way certain important chemicals are processed in the body. Fabry disease is rare; it is found in roughly 1 in 117,000 people. Fabry disease is believed to be rare in India; however, its true prevalence is not known. It is very likely that its prevalence in India is severely underestimated in part due to lack of access to diagnostic testing as well as a lack of awareness about the disease. In the case of Fabry disease, cells store up a fatty substance called globotriaosylceramide (pronounced glow-bow-try-oh-sill-ser-ah-mide) or GL-3. Over time, excessive build-up of GL-3 in some cell types can cause damage (sometimes severe) in tissues throughout the body. What causes GL-3 build-up? With Fabry disease, the body doesn’t produce enough functional alphaGAL to break down the GL-3. Because it is not broken down, the GL-3 accumulates in cell lysosomes. Too much GL-3 accumulation eventually leads to cell damage. problems in the heart, kidneys, skin, brain, and gastrointestinal system. Since many of these symptoms can also be found in other diseases, Fabry disease may not be suspected, and diagnosis may be delayed. Many people may actually go decades before getting diagnosed. Fabry disease runs in families Fabry disease is an inherited disorder. The gene that causes Fabry is passed down from a parent to his or her children. If one person in a family has Fabry disease, other family members (including siblings, children, parents, aunts, uncles, and cousins) may also be at risk. This makes Fabry very much a family disease - not just immediate family, but extended family as well. Fabry disease is considered to be X-linked, which means that the defective gene is located on the X chromosome, and therefore is inherited through the mother. Inheriting Fabry disease Fabry disease can affect anyone who inherits the defective gene: that means both males and females of any ethnic group. The degree to which a person experiences the symptoms of Fabry disease depends on the amount of alpha-GAL enzyme they have. Why diagnosis is often delayed Fabry disease is associated with a wide range of symptoms, including 1 Getting Diagnosed How is Fabry Disease Diagnosed? Recognizing Fabry disease Many of the symptoms of Fabry disease are also common to other diseases, which may make diagnosis difficult. In addition, the symptoms of Fabry disease can occur differently for every individual. Each person with Fabry may have all or only a few of the typical signs and symptoms or may experience symptoms at different times throughout life. That's why it's important to discuss symptoms and risk factors, as well as whether there are other family members with known or suspected Fabry disease, with your doctor. Symptom type Pain Description Acroparesthesia Chronic burning or tingling, primarily in hands and feet Fabry crises Episodes of excruciating burning pain Fatigue Diagnosing Fabry disease Fabry disease is relatively easy to diagnose once suspected. In males, a lack of alpha-GAL activity shows they have inherited the defective gene. Males can usually be diagnosed through a blood test called an enzyme assay that measures the amount of alphaGAL in the blood. Females, however, can have normal amount of alpha-GAL and still carry the defective gene. Since the X-inactivation pattern may be different in different organs such as the heart or kidney, females may have one or more severely affected organs, but still have nearly normal alpha-GAL in their blood. For this reason, a genetic test is needed for an accurate diagnosis. Symptom type Hearing problems Gastrointestinal problems Tiring quickly from exercise Z Z Temperature regulation problems Skin problems 2 • Manifestations vary even among patients from the same family. • Patients may present to and be identified by a number of specialists like nephrologists, neurologists, ENT doctors, cardiologists etc. Description Ringing in ears or hearing loss Nausea Pain after eating Central nervous system problems Headache Dizziness/vertigo Bad memory/trouble thinking clearly Inability to sweat, or overheating Angiokeratomas Reddish-purple spots appear mostly on lower belly and thighs Patients with Fabry disease may present to a range of medical specialties Diarrhea Low energy Excessive need for sleep Z The importance of getting tested If you have or someone you care for has Fabry disease symptoms, your doctor can help you decide whether to get tested for Fabry disease. If someone in your extended family has been diagnosed with Fabry disease, a genetic counselor can help you determine the chances that you or your children may carry the defective gene. Because Fabry disease is progressive, early intervention is important. Speak with your doctor or a genetic counselor about testing for Fabry disease. Irregular heartbeats Thumping in chest Emotional problems Depression or anxiety 3 Fabry Disease Progression Children and Fabry Disease Fabry Disease at different ages Fabry disease and your children A family disease that can worsen over time Over many years, as GL-3 slowly builds up in the walls of blood vessels and other tissues, it is associated with progressive or increasing damage. Major organ systems involving the heart, kidney, and brain may eventually stop functioning properly, causing life-threatening problems. The most serious problems in Fabry disease usually occur in the fourth or fifth decade of life. However, signs and symptoms usually appear much earlier. If the disease is recognized early, doctors can begin exploring disease management options. Female Fabry patients sometimes worry more about the condition's potential effect on their children than about its impact on their own lives. However, the good news is that not all children of women with Fabry disease inherit the disease, and that effective treatment is available for those who do. Symptoms throughout different stages of life Fabry disease causes a variety of symptoms, many of which may be mistaken for those of other diseases. Therefore, diagnosis can be very challenging and may be delayed for years or even decades. Yet early diagnosis is important. attributed to other diseases. Being aware of the types of symptoms children may experience can help lead to early recognition of the disease. Fabry disease in adolescents Teenagers may experience additional signs and symptoms. Gastrointestinal problems, skin rash, and fatigue tend to become more common in adolescence. Fabry disease in adults By the time a person with Fabry disease has reached adulthood, significant build-up of GL-3 in the cells may have occurred, and new signs and symptoms related to organ damage may appear. Childhood Symptoms This means that on average, half of her children will NOT inherit the condition. Acroparesthesia Hypohidrosis/anhidrosis Recurrent fever Heat and cold intolerance Psychosocial manifestations Proteinuria Gastrointestinal distress Angiokeratomas Fatigue Renal insufficiency Neurological complications Cerebrovascular disease Cardiac dysfunction Hearing loss and tinnitus 4 Adulthood If a female Fabry patient has a normal copy of GLA (the gene that, if defective, causes Fabry disease) on one X chromo-some and a Fabry-affected copy on the other, she has a 50% chance with each pregnancy of passing the defective gene down. Episodic pain crises Corneal and lenticular opacities Fabry disease in children Although GL-3 may begin accumulating even before birth, signs and symptoms of accumulation may not be evident until early to late childhood. Even then, these symptoms may be Adolescence To understand why your children will not necessarily inherit your condition, it's helpful to know how Fabry disease is passed down Women have two X chromosomes. They pass one of these two X chromosomes to each of their children (which one is passed down is determined by random chance). We already have children. Should they be screened for Fabry disease? If your partner has Fabry disease, it is possible that one or more of your children may have inherited it. For this reason, it is very important to talk to a health care provider, genetic counselor, or Fabry patient organisation about family screening. The idea of screening your children for Fabry disease may be very upsetting to you and your partner, especially at first. Both of you may have significant fears about your children's health and its impact on their future; in addition, your partner may struggle with feelings of guilt or even fear that you’ll blame him or her if your children have inherited the disease. 5 Family and Fabry Disease Tracing Fabry Disease in Your Family The importance of understanding your family history The most significant clue to a diagnosis of Fabry disease is whether another person in your family has Fabry disease. Put another way, once there is a diagnosis of Fabry disease in your family, there is a high likelihood of finding the disease in relatives, not just in your generation, but in previous and subsequent generations as well. A genetic counselor can help you and your family determine who should be tested. Early diagnosis is important A diagnosis of Fabry disease in your family means that other relatives are likely to have the disease as well. Testing for Fabry disease allows earlier diagnosis and earlier access to appropriate care. Difficult questions • How will the diagnosis affect your decisions about having children? 6 • Do you tell members of your extended family that they may be at risk, and if so, how do you do so in a way that will help? • How does the diagnosis affect your understanding of your family’s past? If, for example, your grandfather died at a young age of kidney disease, could it have been Fabry disease? There is no one way to answer to these questions. Each family, and each person within the family, must address them for themselves. Talking with Family Members Why they should know about the disease Telling family members about Fabry disease may not be easy. Depending on how close you are with your extended family, you may need some time to think beforehand. Tips on talking with family Since many members of your extended family must be considered at risk (including some you may not even know) tact and sensitivity are required: • Be prepared to explain Fabry disease the best you can. • Be a good listener, since the person you tell will need much understanding. • Respect the privacy of the people you tell. Let them decide who else in their lives needs to know. Supporting a husband or wife with Fabry disease Whether the diagnosis of Fabry disease was known before or after the relationship began, spouses can make a tremendous difference in the lives of people with Fabry disease. Finding the right balance between giving support and carrying on a normal life, between taking care of responsibilities and having fun: these things take commitment and practice. 7 Managing Fabry Disease Treatment Approaches Fabry disease can be treated. Living with a chronic illness like Fabry disease is tough. The good news is that there are a variety of treatments and therapies to help control symptoms and prevent long term damage to your body. Medications • Digestive enzymes before meals, antacids, and prokinetics (medications that help move food though your system) can help improve stomach problems. Lifestyle modifications, medications, and surgical procedures can help manage the condition. • Analgesics such as aspirin, ibuprofen, or anticonvulsants can help reduce pain. Talk to your doctor about your symptoms-he or she may be able to provide treatments that can help you feel better, and help prevent or treat complications. Treatments that can help manage Fabry symptoms and complications Lifestyle changes • Enough rest and daily gentle exercise can help reduce fatigue and improve mood. • A low fat diet and small, frequent meals can help prevent stomach upset after eating. • Emotional support from friends, family or a counselor can help prevent or counter depression. Surgery and other treatments • Dialysis may be needed for severe kidney problems. • Pacemaker insertion, angioplasty, or heart bypass surgery may be needed for severe heart problems. Discuss your options with your physician. 8 Enzyme Replacement Therapy : Fabrazyme • Medications can help manage and treat heart problems. • Blood thinners can help prevent blood clots and strokes. • Antidepressants and antianxiety medications can help improve mood. What about Fabry-specific treatment? Until a few years ago, there was no specific treatment for Fabry disease. Doctors could only treat the symptoms and complications of the disease. Fortunately, enzyme replacement therapy, like Fabrazyme, is now available to treat Fabry disease. What is Fabrazyme? Fabrazyme is an enzyme created by genetic technology that is identical to alphagalactosidase A-the enzyme that people with Fabry disease are missing. Fabrazyme is administered through a vein and can replace the missing enzyme in people with Fabry disease, acting like the natural enzyme inside the body. How is Fabrazyme administered? Fabrazyme enzyme replacement therapy is injected through a vein directly into the bloodstream every 2 weeks usually at a special infusion centre, or sometimes it’s possible to receive infusions at home. Your infusions will take 4 or 5 hours at first, however, your doctor may be able to decrease your infusion time to about 2 hours (or as little as 90 minutes) once your body becomes used to treatment. During the infusion, you can read a book, catch up on email, or take a nap. You can walk around and visit the restroom if you need to. How does Fabrazyme work? The symptoms and complications of Fabry disease are caused by a buildup of a substance (called globotriaosylceramide-or GL-3) in the cells of the body. This substance is ordinarily broken down and removed by the enzyme alpha-galactosidase Athe enzyme that is missing in those people with Fabry disease. By replacing this missing enzyme, Fabrazyme can help clear existing build-up and may prevent the further build-up of GL-3, reducing the risk of serious complications such as stroke, kidney failure, or heart failure. The treatment replaces the alphagalactosidase A enzyme that's missing in people with Fabry disease. Physicians often recommend a combination of lifestyle changes and medication-in addition to enzyme replacement therapy-to best manage Fabry disease. 9 Managing Your Symptoms GL-3 builds up in the cells of the heart, the kidneys, and the blood vessels that feed the brain Both symptom management and enzyme replacement therapy can play a role in the treatment of people with Fabry disease. Since Fabry disease affects many organ systems it is possible that you may see several types of doctors. For some people, managing the symptoms of Fabry disease can mean making changes in your lifestyle. This may include avoiding or preparing for certain activities that may make symptoms worsen. Some people may require medications on a daily basis for pain or gastrointestinal symptoms. Fabrazyme helps GL-3 break down With ongoing use, Fabrazyme therapy may help reduce the risk of organ damage and other serious complications-such as heart attack, kidney failure, and stroke caused by Fabry disease. It is best to start therapy as early as possible, because Fabrazyme cannot necessarily heal existing damage that already occurred before treatment was started. 10 Clinical data show that treatment with Fabrazyme reduces the risk of cardiac, renal, and cerebrovascular events by 61% as compared to placebo. Here is a brief look at management approaches: 60 Placebo N=12 events/27 patients) 50 40 61% 30 Probability of Event (%) Does it matter when I start Fabrazyme therapy? You should consider starting Fabrazyme therapy when you are diagnosed with Fabry disease-it can help clear GL-3 build-up from the body and reduce the risk of future damage and complications at almost any stage of the Fabry disease process. Risk Reduction Fabrazyme N=13 events/47 patients) Kidney problems GL-3 accumulation in the kidneys may lead to impaired function and may ultimately lead to kidney failure. If the problems are severe, dialysis (a system where an external machine filters the blood) or a kidney transplant may be required. 20 10 5 10 Time in study (months) 15 20 25 30 35 40 Heart problems GL-3 accumulation can lead to several different types of heart problems, including enlarged heart and heart valve abnormalities. Heart problems are usually managed with medication, depending on how severe they are. If medication is not sufficient, other steps may be taken. Complications in the brain Significant GL-3 accumulation can thicken small arteries in the brain. To help reduce the risk of stroke, physicians may prescribe medication. Pain management Pain is common in people with Fabry disease. Your doctor may recommend ways of reducing the frequency and severity of pain due to Fabry disease, such as: • Avoiding certain strenuous activities • Preparing in advance for changing weather conditions • Conserving your energy with frequent naps or breaks • Increasing your intake of water or other liquids • Your doctor may prescribe medication to help alleviate pain Skin problems Doctors can remove the skin rashes (angiokeratomas) commonly associated with Fabry disease. Gastrointestinal symptoms Gastrointestinal symptoms may include stomach pain, vomiting, nausea, and diarrhea. Your doctor may recommend a low-fat diet, or alternatively, may recommend medication. 11 Taking Care Psychosocial symptoms Patients with Fabry disease may demonstrate psychosocial trends common to other chronic illnesses, including clinical depression, denial of clinical symptoms, and feelings of alienation and loneliness. Emotional Support is Important Emotional support and family counseling can be an important part of your care. Depression and/or denial are common, as is 12 guilt about passing on the defective gene to children. Family and individual counseling can be important for people living with Fabry disease and their families. Contact with other people and families struggling with similar issues may help with feelings of isolation, loneliness, and despair. Several organizations and medical centers offer websites, newsletters, support groups, and information on Fabry disease. Monitoring Progress Just as Fabry disease affects different people differently, responses to treatment will vary from person to person, as well. Your physician will likely want to see you regularly to check how you are responding to Fabrazyme treatment and to assess your overall health. Your physician may also have recommendations about nutritional changes in your diet or changes in exercise or activity levels. Your well-being is important Taking care of yourself means more than just getting good medical care. It also means making your own well-being a priority. Experiment with different approaches to find the ways of reducing stress, communicating about the impact of Fabry disease, and managing your time and energy that work best for you. Lifestyle Changes • Avoidance of stimuli that cause patin, such as stress, physical exertion, heat or sun exposure, and extreme temperature changes • Avoidance of smoking, since smoking can exacerbate breading symptoms. Some Important Tips Try to schedule your infusions for the same time and day of the week. If you're planning a long trip, tell you health care provider as soon as possible. He or she may be able to help you schedule your infusions in the place you'll be visiting. Dress in easily-removable layers to avoid overheating. Anticipate busy periods, and plan ahead for their possible impact on your treatment schedule. Eat a low-fat diet, especially if you have stomach problems. Low protein diet for kidney problems. Increased fluid intake in hot weather and during physical activity to minimize the likelihood of heart exhaustion. Try your best to get plenty of sleep. When you're feeling down, reach out to a friend or family member, or contact a Fabry patient organisation for support. Remember, you are not alone! 13 Additional information on Fabry disease can be found at the following websites Recommended schedule of tests Frequency Recommended test Every 6 months Every 12 months Every 24-36 months At time of event or therapy change General Medical history Family history Physical exam Weight Vital signs (blood pressure, pulse, etc) Lipid panel • • • • • • • • http://www.fabrycommunity.com/ www.fabry.org www.fabrydisease.org www.kidney.org www.nefsg.org www.geneticalliance.org www.ninds.nih.gov www.rarediseases.org Heart (cardiac function) Echocardiogram (ECHO) Electrocardiogram (ECG) 24-hr Holter monitoring Kidney (renal function) * Serum creatinine and/or glomerular filtration rate Blood urea nitrogen (BUN) Urinary protein excretion Brain Magnetic resonance imaging (MRI) Lungs Spirometry ** Stomach Clinical evaluation for symptoms such as nausea and diarrhea Eyes (vision) Slit lamp exam Ears (hearing) *** Audiologic evaluations Nerves Evaluation for sweating, heat/cold intolerance, and pain level Quality of life and emotional/psychological state Questionnaires * Annual 24-hr Holter monitoring is recommended for all male patients ≥ 30 yrs of age and all female patients ≥ 40 yrs of age, for any patient whose ECG is abnormal, or if/when symptoms arise. ** Spirometry should be performed annually if results are abnormal. ***Slit lamp exam should be performed annually if certain retinal problems are present. 14 15 16 17