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 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.
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
Understanding Fabry disease
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 and
accumulate in different parts of
the body, leading to cell and
Fabry disease is caused by the
mutation of the GLA gene, located
on the X-chromosome. This gene
is responsible for the production
of a specific enzyme,
alpha-galactosidase A, 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
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.
Progressive damage to vital organs
occurs over several decades. It
results in end-stage kidney disease
and/or life-threatening complications
affecting 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.
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.
Genetic counselling can help people cope with some of the emotions and implications 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
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.
Neuropathic pain, defined as sensations of burning, shocks or shooting pain, tingling,
pins and needles, stabbing, and/or numbness in the hands and feet. Pain may be permanent
or occur randomly, and may be triggered by heat or cold, a fever, and/or physical activity.
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.
Premature death due to vital organ disease
resulting in end-stage renal disease and/or
life-threatening complications affecting 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).
Neuropathic pain – pain usually associated with nerves in the extremities
– is one of the ‘classic’ symptoms of Fabry disease.
For many people with Fabry disease, pain is one of the most debilitating symptoms
affecting their quality of life, and is an early indicator of the disease.
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.
Fabry disease inheritance pattern
Parts of the body affected by 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.
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.
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.
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)
Psychiatrists (specialists in mental illness)
Psychologists (specialists in human emotions and behavior)
Speech and language therapists
How does Fabry disease progress over time?
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 managing 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 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 Fabry disease.
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.
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.
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.
Practical guidance on managing Fabry disease
There are a number of things that people
affected by Fabry disease can do to help
them 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
everyone has access to genetic testing
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.
Fatigue can affect all aspects of life, both mentally and physically, and is a common symptom of Fabry disease.
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.
Reaching out for support
Some people find support group meetings or online forums very valuable 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 to discuss ways of adjusting to a new reality and coping with the challenges that the disease may present.
There are many patient associations that are dedicated to supporting patients and their families to live well with Fabry disease by providing detailed information, practical advice and valuable support.
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
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.
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