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This eBook has been developed by Idorsia Pharmaceuticals Ltd as a resource to help the understanding of Fabry disease. It provides a summary of current information about the disease, the diagnosis procedure and available treatments. It highlights the impact Fabry disease can have on those living with the condition and those around them. It also outlines the strategies people with Fabry disease and their families can use to manage the condition as effectively as possible.
The book is intended for the use of a general audience.
About this eBook
Get Started
“My doctor called me up, had a chat with us as
a family. I felt relief for my son, that at last we knew what was wrong. Then, sort of very scared, once we knew that everyone had got to go for health checks to find out who had got it and that it could cause lots of other problems with the major organs in your body. It was a scary time.”
— Patient
Introduction
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.
Introduction
Understanding Fabry disease
Diagnosis and treatment of
Fabry disease
Burden of Fabry disease
Practical guidance on managing
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
Understanding Fabry disease
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.
What is Fabry disease and what causes it?
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.
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.
What is the role of lipids in the body?
Types of Fabry disease
What is the role of lipids in the body?
Types of Fabry disease
Introduction
Understanding Fabry disease
Diagnosis and treatment of
Fabry disease
Burden of Fabry disease
Practical guidance
on managing
Fabry disease
Introduction
Understanding Fabry disease
Types of Fabry disease
Fabry disease can be divided into a severe, classical form, and a generally milder, non-classical form, which is also called late-onset or atypical variant.
The classical form is often seen in men with little or no functioning of the necessary enzyme to break down Gb3. It starts in childhood and progresses relatively fast. Children with classical Fabry disease typically present with characteristic Fabry symptoms, such as pain in the hands and feet, skin and digestive problems. Advanced organ symptoms will develop later during adolescence and adulthood, in particular kidney disease, heart disease or stroke.
The non-classical form is characterized by a more variable disease course, in which people are generally less severely affected. Disease manifestations may be limited to a single organ, for example the heart. People with the non-classical form have some enzyme activity left, resulting in slower progression of the disease and typically no symptoms in childhood and adolescence.
What is the role of lipids in the body?
Lipids are fat-like substances such as fatty acids, oils, waxes and steroids. A well-known example is cholesterol.
Lipids are stored naturally in the body’s cells and organs and are vital to their healthy functioning.
What happens in patients with lysosomal storage disorders?
Normally, the body is able to process lipids effectively, which keeps them within healthy levels.
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.
How is Fabry disease inherited?
What is the role of genetic testing?
What is the role of genetic testing?
Fabry disease inheritance pattern
Fabry disease inheritance pattern
What is the role of genetic testing?
A genetic test can help identify if there is a change (mutation) in a particular gene or chromosome.
It is used to confirm a diagnosis of Fabry disease via a blood or tissue sample.
Genetic testing is usually offered to relatives of someone diagnosed with Fabry disease to see if they also have the condition.
Fabry disease inheritance pattern
Genetic counselling can help people cope with some of the emotions and implications of genetic testing.
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.
How common is Fabry disease and who gets it?
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.
Signs and symptoms of Fabry disease
Early onset symptoms
Early onset symptoms
Parts of the body affected by Fabry disease
Parts of the body affected by Fabry disease
Kidneys
Cysts, reduced kidney function, progressive kidney failure
Early onset symptoms
Neuropathic pain.
Decreased or absent sweat production causing discomfort in warm temperatures.
Reddish rash on the skin.
Gastrointestinal problems, such as abdominal pain, diarrhea, bloating and nausea.
Changes to the cornea of the eye, becoming less clear in appearance.
Fatigue.
Headaches and dizziness.
Hearing loss.
Later onset symptoms
Later onset symptoms
Later onset symptoms
Kidney disease: increased proteinuria, renal fibrosis, renal sclerosis leading to end-stage renal disease.
Heart disease: arrhythmias, dyspnea, cardiac ischemia, angina, left ventricular hypertrophy, fibrosis.
Disease of the nervous system: ischemic attacks, strokes and vascular dementia.
“In high school, I remember having some episodes, I just didn’t get it. There was nothing wrong with me that anybody could see… I didn’t know what to
do about it”
— Patient
Introduction
Understanding Fabry disease
Diagnosis and treatment of
Fabry disease
Burden of Fabry disease
Practical guidance on managing
Fabry disease
Diagnosis and treatment of Fabry disease
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?
How is Fabry disease diagnosed?
Family history and prenatal diagnosis
Family history and prenatal diagnosis
How is Fabry disease diagnosed?
Upon a suspicion of Fabry disease, three biological tests can be used to assert a specific diagnosis:
A genetic test will determine whether a disease-causing mutation is present in the GAL gene, which is responsible for Fabry disease. More than 850 individual GLA gene mutations have been identified.
Physical examination: to check for skin reddening, lesions in eyes, irregular heart rhythms and other clues.
An enzymatic test will determine how much α-GalA activity is present in plasma or blood white cells. A reduction in α-GalA activity below a certain level will support a diagnosis of Fabry disease.
A biomarker test will determine how much Gb3 is present in plasma, urine or a skin biopsy. An increase in Gb3 concentration above a certain level will support a diagnosis of Fabry disease.
Clinical and physical examination will include:
CAT scan and echocardiography: to check for an enlarged heart or any other heart or vascular abnormalities.
Ultrasound (or sonogram): to scan inside the body using high-frequency sound waves.
Renal function measures: to check the ability of the kidneys to function properly based on biochemical measures in the blood and urine.
MRI scan: to detect changes in the brain.
Neurologic examination: to understand any potential damage caused by stroke lesions.
Family history and prenatal diagnosis
For an inherited disease like Fabry disease, the diagnosis of one family member can greatly speed up the diagnosis of others in the family.
If there is a history of Fabry disease or a new diagnosis within the family, it is recommended that all blood relatives are tested for the disease.
It is even possible to test for Fabry disease before birth, as a prenatal diagnosis can be made by using samples of cells from the unborn baby.
There is specialist support and counselling available to help families and expectant mothers through the process of genetic testing.
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.
What treatments are available for Fabry disease?
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.
Chaperone
therapy
Chaperone
therapy
Enzyme replacement therapy
How does Fabry disease progress over time?
How does Fabry disease progress over time?
How does Fabry disease progress over time?
Chaperone therapy
A pharmacological chaperone is a small molecule that is designed to enhance the enzymatic activity in cells of some people with Fabry disease that carry certain mutations called 'amenable' mutations.
Chaperone therapy can be administered to adolescents aged 16—17 years and adults with Fabry disease.
Chaperone therapy is an oral therapy administered every other day.
Enzyme replacement therapy
Enzyme Replacement Therapy (ERT) uses a genetically engineered form of the enzyme — a protein — that is missing or malfunctioning in Fabry disease.
ERT can be administered to children and adults with Fabry disease.
Enzyme replacement therapy
ERT requires intravenous infusions every two weeks.
The aim of ERT is to help relieve certain symptoms and to prevent progression of damage to important organs, such as the kidney and the heart.
After an initial series of infusions at the hospital, many people receive infusions at their own home, given by a nurse or caregiver. These are more convenient and less disruptive to daily life.
The aim of the treatment is to help relieve certain symptoms and to prevent progression of damage to important organs, such as the kidney and the heart.
Symptom management
Symptom management
Symptom management
Several options are available to help manage the symptoms of Fabry disease. These include:
Over-the-counter and prescription painkillers to alleviate neuropathic pain.
Medications that help to preserve/protect the kidney function.
Dialysis and kidney transplantation in cases of advanced renal failure.
Treatments that prevent or alleviate irregular heart rhythm.
Heart transplantation in cases of advanced congestive heart failure.
Blood thinners, such as aspirin and warfarin, to reduce the risk of stroke.
Physiotherapy to support rehabilitation post-stroke or post-heart-attack.
Which healthcare professionals are involved in the treatment of Fabry disease
Which healthcare professionals are involved in the treatment of Fabry disease
Which healthcare professionals are involved in the treatment of Fabry disease
Treatment for Fabry disease is usually carried out under the care of a specialist or a team of multidisciplinary specialists. The type of specialist will vary according to the age of the patient and the type of symptoms they have. A range of healthcare professionals may be involved in the care of patients with Fabry disease, including:
Nephrologists (kidney specialists)
Cardiologists (heart specialists)
Hepatologists (liver specialists)
Gastroenterologists (specialists in digestive disorders)
Pediatricians (specialists in children’s health)
Neurologists (specialists in the nervous system)
Nurse specialists
Psychiatrists (specialists in mental illness)
Psychologists (specialists in human emotions and behavior)
Physiotherapists
Occupational therapists
Speech and language therapists
Geneticists
“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
Introduction
Understanding Fabry disease
Diagnosis and treatment of Fabry disease
Burden of Fabry disease
Practical guidance on managing
Fabry disease
Burden of Fabry disease
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.
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.
Coming to terms with the diagnosis
Many people will have never heard of Fabry disease, but may be relieved to have a name for their condition after potential years of frustration seeking a diagnosis.
It is challenging to come to terms with the diagnosis of Fabry disease, and people’s initial reactions may change over time as they learn more about the disease and adjust to the realities of living with it.
As Fabry disease is inherited, some parents may feel a misplaced sense of guilt for passing the disease on to their child and some may fear further diagnoses within their family.
The emotional, physical and financial demands of any serious disease may put a strain on family life or relationships.
It is important for those affected to be aware of support and counselling services available to help them come to terms with a diagnosis, as advised by a local patient association of medical team.
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.
“You try to stay positive... but it’s very emotional and it drains you.”
— Patient
Diagnosis and treatment of Fabry disease
Burden of Fabry disease
Practical guidance on managing Fabry disease
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.
Introduction
Understanding Fabry disease
Diagnosis and treatment of Fabry disease
Burden of Fabry disease
Practical guidance on managing
Fabry disease
Practical guidance on managing
Fabry disease
Managing fatigue
Managing pain
Managing pain
Pain can be one of the most difficult symptoms of Fabry disease to manage day-to-day and can cause of cycle of distress and disability.
Given its significant impact on quality of life, reducing pain is one of the main objectives of Fabry disease treatment and a measure of its success.
In addition to pain medication, it can be helpful to:
The pain cycle
Managing fatigue
Fatigue can affect all aspects of life, both mentally and physically, and is a common symptom of Fabry disease.
Resting before and after activities, asking others to help with chores, planning ahead and being realistic about what needs to be done by when, can all help to combat fatigue.
Managing pain
As it is an ‘invisible’ symptom, it is important that people living with Fabry disease are honest about how they are feeling and take steps to manage their fatigue.
- Avoid certain strenuous activities
- Prepare in advance for changing weather conditions
- Increase your intake of water and other liquids
- Seek ways of relaxing and breaking negative thought patterns
Managing fatigue
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.
Reaching out for support
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 fabrynetwork.org/fin-members
Disclaimer
This resource has been developed by Idorsia Pharmaceuticals Ltd in order to provide an environment to deliver a better understanding of Fabry disease and to pool information regarding the disease, the diagnosis procedure, available treatments and the impact it could have on the life of someone diagnosed with Fabry disease. The resource is for use by a general audience.
The information in this resource is not intended as a substitute for advice/treatment by a physician, whose instructions should always be followed. Neither does the information provided constitute an alternative to advice from a doctor or a pharmacist and should not be used on its own to produce a diagnosis or to commence or cease a particular treatment.
The links provided are for informational purposes only; they do not constitute an endorsement or an approval from Idorsia of the services or opinions of the
corporation, organization or individual. Idorsia bears no responsibility for the accuracy, legality or content of the external sites or subsequent links. You are requested to contact the respective external site for answers to questions regarding its content.
The information provided is valid on the publication date but may be subject to further modifications. Even though Idorsia aims to provide accurate and up to date information at all times, please acknowledge that the present resource is made available “as is”. Idorsia does not give any warranty or representation, whether expressly stated or implied, of any kind related to the comprehensiveness, usefulness, reliability or timelines of the content of this resource. Idorsia cannot be held liable for any direct or indirect damage of a material or non-material nature that might be caused by the use or non-use of the information presented.
Disclaimer
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About this eBook
About this eBook
This eBook has been developed by Idorsia Pharmaceuticals Ltd as a resource to help the understanding of Fabry disease. It provides a summary of current information about the disease, the diagnosis procedure and available treatments. It highlights the impact Fabry disease can have on those living with the condition and those around them. It also outlines the strategies people with Fabry disease and their families can use to manage the condition as effectively as possible.
The book is intended for the use of a general audience.
Get Started
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“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
Understanding Fabry disease
What is the role of genetic testing?
Fabry disease inheritance pattern
Fabry disease inheritance pattern
CLOSE
What is the role of
genetic testing?
A genetic test can help identify if there is a change (mutation) in a particular gene or chromosome.
CLOSE
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.
How is Fabry disease inherited?
Types of Fabry disease
What is the role
of lipids in the body?
What happens in patients with lysosomal storage disorders?
What is the role of lipids in the body?
Lipids are fat-like substances such as fatty acids, oils, waxes and steroids. A well-known example is cholesterol.
Lipids are stored naturally in the body’s cells and organs and are vital to their healthy functioning.
Normally, the body is able to process lipids effectively, which keeps them within healthy levels.
CLOSE
Types of Fabry disease
Fabry disease can be divided into a severe, classical form, and a generally milder, non-classical form, which is also called late-onset or atypical variant.
The classical form is often seen in men with little or no functioning of the necessary enzyme to break down Gb3. It starts in childhood and progresses relatively fast. Children with classical Fabry disease typically present with characteristic Fabry symptoms, such as pain in the hands and feet, skin and digestive problems. Advanced organ symptoms will develop later during adolescence and adulthood, in particular kidney disease, heart disease or stroke.
The non-classical form is characterized by a more variable disease course, in which people are generally less severely affected. Disease manifestations may be limited to a single organ, for example the heart. People with the non-classical form have some enzyme activity left, resulting in slower progression of the disease and typically no symptoms in childhood and adolescence.
CLOSE
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.
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.
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.
What is Fabry disease and what causes it?
Understanding Fabry disease
Introduction
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.
“My doctor called me up, had a chat with us as a family. I felt relief for my son, that at last we knew what was wrong. Then, sort of very scared, once we knew that everyone had got to go for health checks to find out who had got it and that it could cause lots of
other problems with the major organs in your body. It was a scary time.”
— Patient
Introduction
It is used to confirm a diagnosis of Fabry disease via a blood or tissue sample.
Genetic testing is usually offered to relatives of someone diagnosed with Fabry disease to see if they also have the condition.
Genetic counselling can help people cope with some of the emotions and implications of genetic testing.
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 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.
How common is Fabry disease and who gets it?
Early onset symptoms
Parts of the body affected by Fabry disease
Parts of the body affected by Fabry disease
CLOSE
Early onset symptoms
Neuropathic pain.
CLOSE
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.
Signs and symptoms of Fabry disease
Decreased or absent sweat production causing discomfort in warm temperatures.
Reddish rash on the skin.
Gastrointestinal problems, such as abdominal pain, diarrhea, bloating and nausea.
Changes to the cornea of the eye, becoming less clear in appearance.
Fatigue.
Headaches and dizziness.
Hearing loss.
Life
expectancy
Life expectancy
Premature death due to vital organ disease resulting in end-stage renal disease and/or life-threatening complications that affect the blood supply to heart and brain.
CLOSE
According to data from the Fabry Registry, the life expectancy of men with Fabry disease was 58.2 years, compared with 74.7 years in the general population. The life expectancy of women with Fabry disease at birth was 75.4 years, compared with 80.0 years in the general population (as of August 2008).
Later onset symptoms
Kidney disease: increased proteinuria, renal fibrosis, renal sclerosis leading to end-stage renal disease.
CLOSE
Later onset symptoms
Heart disease: arrhythmias, dyspnea, cardiac ischemia, angina, left ventricular hypertrophy, fibrosis.
Disease of the nervous system: ischemic attacks, strokes and vascular dementia.
In high school, I remember having some episodes, I just didn’t get it. There was nothing wrong with me that anybody could see… I didn’t know what to do about it”
— Patient
Diagnosis and treatment of Fabry disease
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.
Diagnosis and treatment of Fabry disease
How is Fabry disease diagnosed?
Upon a suspicion of Fabry disease, three biological tests can be used to assert a specific diagnosis:
CLOSE
How is Fabry disease diagnosed?
A genetic test will determine whether a disease-causing mutation is present in the GAL gene, which is responsible for Fabry disease. More than 850 individual GLA gene mutations have been identified.
An enzymatic test will determine how much α-GalA activity is present in plasma or blood white cells. A reduction in α-GalA activity below a certain level will support a diagnosis of Fabry disease.
A biomarker test will determine how much Gb3 is present in plasma, urine or a skin biopsy. An increase in Gb3 concentration above a certain level will support a diagnosis of Fabry disease.
Clinical and physical examination will include:
Physical examination: to check for skin reddening, lesions in eyes, irregular heart rhythms and other clues.
CAT scan and echocardiography:
to check for an enlarged heart or any other heart or vascular abnormalities.
Ultrasound (or sonogram): to scan inside the body using high-frequency sound waves.
Renal function measures: to check the ability of the kidneys to function properly based on biochemical measures in the blood and urine.
MRI scan: to detect changes in the brain.
Neurologic examination: to understand any potential damage caused by stroke lesions.
Family history and prenatal diagnosis
For an inherited disease like Fabry disease, the diagnosis of one family member can greatly speed up the diagnosis of others in the family.
CLOSE
Family history and prenatal diagnosis
If there is a history of Fabry disease or a new diagnosis within the family, it is recommended that all blood relatives are tested for the disease.
It is even possible to test for Fabry disease before birth, as a prenatal diagnosis can be made by using samples of cells from the unborn baby.
There is specialist support and counselling available to help families and expectant mothers through the process of genetic testing.
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.
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:
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.
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.
Enzyme replacement therapy
How does Fabry disease progress over time?
How does Fabry disease progress over time?
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Enzyme replacement therapy
Enzyme Replacement Therapy (ERT) uses a genetically engineered form of the enzyme — a protein — that is missing or malfunctioning in Fabry disease.
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ERT can be administered to children and adults with Fabry disease.
ERT requires intravenous infusions every two weeks.
The aim of ERT is to help relieve certain symptoms and to prevent progression of damage to important organs, such as the kidney and the heart.
After an initial series of infusions at the hospital, many people receive infusions at their own home, given by a nurse or caregiver. These are more convenient and less disruptive to daily life.
Chaperone therapy
Chaperone therapy
A pharmacological chaperone is a small molecule that is designed to enhance the enzymatic activity in cells of some people with Fabry disease that carry certain mutations called 'amenable' mutations.
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Chaperone therapy can be administered to adolescents aged 16—17 years and adults with Fabry disease.
Chaperone therapy is an oral therapy administered every other day.
The aim of the treatment is to help relieve certain symptoms and to prevent progression of damage to important organs, such as the kidney and the heart.
Symptom management
Symptom management
Several options are available to help manage the symptoms of Fabry disease. These include:
Over-the-counter and prescription painkillers to alleviate neuropathic pain.
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Medications that help to preserve/protect the kidney function.
Dialysis and kidney transplantation in cases of advanced renal failure.
Treatments that prevent or alleviate irregular heart rhythm.
Heart transplantation in cases of advanced congestive heart failure.
Blood thinners, such as aspirin and warfarin, to reduce the risk of stroke.
Physiotherapy to support rehabilitation post-stroke or post-heart-attack.
Which healthcare professionals are involved in the treatment of Fabry disease
Which healthcare professionals are involved in the treatment of Fabry disease
Treatment for Fabry disease is usually carried out under the care of a specialist or a team of multidisciplinary specialists. The type of specialist will vary according to the age of the patient and the type of symptoms they have.
A range of healthcare professionals may be involved in the care of patients with Fabry disease, including:
Nephrologists (kidney specialists)
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Cardiologists (heart specialists)
Hepatologists (liver specialists)
Gastroenterologists (specialists in digestive disorders)
Pediatricians (specialists in children’s health)
Neurologists (specialists in the nervous system)
Nurse specialists
Psychiatrists (specialists in mental illness)
Psychologists (specialists in human emotions and behavior)
Physiotherapists
Occupational therapists
Speech and language therapists
Geneticists
“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
Burden of Fabry disease
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.
Burden of Fabry disease
Coming to terms with the diagnosis
Many people will have never heard of Fabry disease, but may be relieved to have a name for their condition after potential years of frustration seeking a diagnosis.
It is challenging to come to terms with the diagnosis of Fabry disease, and people’s initial reactions may change over time as they learn more about the disease and adjust to the realities of living with it.
As Fabry disease is inherited, some parents may feel a misplaced sense of guilt for passing the disease on to their child and some may fear further diagnoses within their family.
The emotional, physical and financial demands of any serious disease may put a strain on family life or relationships.
It is important for those affected to be aware of support and counselling services available to help them come to terms with a diagnosis, as advised by a local patient association of medical team.
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.
Impact on children
“You try to stay positive... but it’s very emotional and it drains you.”
— Patient
Practical guidance on managing
Fabry disease
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.
Practical guidance on managing Fabry disease
Managing
pain
Managing fatigue
Managing pain
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Managing fatigue
Fatigue can affect all aspects of life, both mentally and physically, and is a common symptom of Fabry disease.
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Pain can be one of the most difficult symptoms of Fabry disease to manage day-to-day and can cause of cycle of distress and disability.
Given its significant impact on quality of life, reducing pain is one of the main objectives of Fabry disease treatment and a measure of its success.
In addition to pain medication, it can be helpful to:
- Avoid certain strenuous activities
- Prepare in advance for changing weather conditions
- Increase your intake of water and other liquids
- Seek ways of relaxing and breaking negative thought patterns
The pain cycle
As it is an ‘invisible’ symptom, it is important that people living with Fabry disease are honest about how they are feeling and take steps to manage their fatigue.
Resting before and after activities, asking others to help with chores, planning ahead and being realistic about what needs to be done by when, can all help to combat fatigue.
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.
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 fabrynetwork.org/members
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.
Disclaimer
This resource has been developed by Idorsia Pharmaceuticals Ltd in order to provide an environment to deliver a better understanding of Fabry disease and to pool information regarding the disease, the diagnosis procedure, available treatments and the impact it could have on the life of someone diagnosed with Fabry disease.
The resource is for use by a general audience.
The information in this resource is not intended as a substitute for advice/treatment by a physician, whose instructions should always be followed. Neither does the information provided constitute an alternative to advice from a doctor or
a pharmacist and should not be used on its own
to produce a diagnosis or to commence or cease
a particular treatment.
The links provided are for informational purposes only; they do not constitute an endorsement or an approval from Idorsia of the services or opinions of the corporation, organization or individual. Idorsia bears no responsibility for the accuracy, legality or content of the external sites or subsequent links. You are requested to contact the respective external site for answers to questions regarding
its content.
The information provided is valid on the publication date but may be subject to further modifications. Even though Idorsia aims to provide accurate and up to date information at all times, please acknowledge that the present resource is made available “as is”. Idorsia does not give any warranty or representation, whether expressly stated or implied, of any kind related to the comprehensiveness, usefulness, reliability or timelines of the content of this resource. Idorsia cannot be held liable for any direct or indirect damage of a material or non-material nature that might be caused by the use or non-use of the information presented.
Disclaimer
Life expectancy
Premature death due to vital organ disease resulting in end-stage renal disease and/or life-threatening complications that affect the blood supply to heart and brain.
According to data from the Fabry Registry, the life expectancy of men with Fabry disease was 58.2 years, compared with 74.7 years in the general population. The life expectancy of women with Fabry disease at birth was 75.4 years, compared with 80.0 years in the general population (as of August 2008).
Life
expectancy
Life
expectancy
Based on MacDermont FD. J Med Genetn 38:750-760
Parts of the body affected
by Fabry disease
Digestive Tract
Abdominal pain, constipation, diarrhea, and nausea
Skin
Dark red spots or rashes, burning/ tingling sensations, sensitivity to temperature and profuse sweating
Brain
Strokes (in severe cases), and dizziness
Heart
Irregular or abnormal heart rhythm and other problems
Ears
Tinnitus, hearing loss, and vertigo
Eyes
The appearance of the eyes changes
Neuropathic pain
Pain resulting from damage to or dysfunction of the nervous system