Download Living with Fabry Disease

Living with
Fabry Disease
A guide for patients, parents,
relatives, and friends
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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
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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
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• 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
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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
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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.
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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?
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• 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.
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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.
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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.
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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.
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