MyResults.Org

Fabry Disease

Text Size:

Overview

What is Fabry disease?
Fabry disease is a rare inherited disease caused by changes to a gene called GLA. GLA is involved in breaking-down fatty substances (called globotriaosylceramide) in your cells. When these fatty substances fail to break down, they can build up at different organs in the body - particularly in blood vessels, tissues and organs. This can lead to a wide range of symptoms, including severe pain in hands and feet, discolored red/blue marks on the skin, an inability to sweat (or occasionally too much sweating), kidney problems, heart problems, stomach problems, neurological problems, ringing in the ears (tinnitus), hearing loss, and/or cloudiness in the eye. Fabry disease is one of many diseases known as lysosomal storage disorders, which all have in common the feature that they cannot break down certain types of fat molecules.

Fabry disease in an X-linked condition, meaning it is caused by a change in the X-chromosome (where the GLA gene is located). Men have only one X-chromosome, while women have two. For this reason, the disease is usually more severe in men (women typically have one 'normal' version of GLA, on the other X-chromosome). Men usually begin to show symptoms at about 12-13 years of age (versus about 19 for women), and also tend to have more severe symptoms (see Mehta, Beck, and Sunder-Plassmanns, 2006).

The main treatment for Fabry disease is enzyme replacement therapy (ERT), which is used to prevent symptoms. If symptoms already exist - such as pain or organ-problems (e.g. heart, kidney, brain, skin, ears or eyes) - treatments are specific to each patient. If a person has Fabry disease, or is found to have a genetic change that increases risk of developing the condition, they should have regular health checks to monitor symptoms.

Fabry disease is also known as Fabry's disease, Anderson-Fabry disease, angiokeratoma corporis diffusum, alpha-galactosidase A deficiency, angiokeratoma diffuse, ceramide trihexosidase deficiency, GLA deficiency, and hereditary dystopic lipidosis.

Changes in the <i>GLA</i>gene are known to cause Fabry disease. Less than 1 in 40,000 people develop Fabry disease. However, for males with changes in the <i>GLA</i> gene linked to Fabry disease, all will develop the condition. Similarly, 70 in 100 females with a known <i>GLA</i> risk gene will develop symptoms. Image created by Iconarray.com. Risk Science Center and Center for Bioethics and Social Sciences in Medicine, University of Michigan. Accessed 2016-09-16.

What is the genetic test?
Genetic testing allows us to identify people at risk of developing Fabry disease. Changes in the GLA gene are known to cause the condition, and genetic testing allows us to identify those most at risk. The American College of Medical Genetics recommends testing and returning results for GLA/Fabry disease. The genetic test can indicate if a person carries a genetic change associated with the disease, as well as other conditions discussed on this website.

How will this affect my health care?
When a person tests positive for a genetics risk of developing Fabry disease, it is recommended that they receive diagnosis and health management as soon as possible. Genetic testing can be offered to family members as well. Consulting with a clinical geneticist or genetic counselor can help with health care decisions. In addition, deep testing for symptoms associated with Fabry disease is recommended - this should involve the following:

  • History: A medical professional should take a personal and family history, focusing in particular on organ problems, and pain.
  • Screening assessments: This involves testing each organ system, including kidneys, heart, brain, skin, stomach.intestines, eyes, and ears.
  • Annual health checks: Follow-up regularly for health checks, including testing kidney function, heart function, and hearing tests
  • MRI brain scans: Magnetic resonance imaging (MRI) scan every two years to check for brain problems
  • MRA blood vessel scans: Magnetic resonance angiogram (MRA) scan every two years to test for problems related to blood vessels


As discussed under Treatment, if a person develops Fabry disease, the main treatment is enzyme replacement therapy (ERT). In addition, treatments for symptoms, such as pain or organ-problems (e.g. heart, kidney, brain, skin, ears or eyes) are specific to each patient.

Who is at risk?
Fabry is very rare, and affects less than 1 in 40,000 people. However, if a person has a relative with Fabry disease (or a relative with a risk gene that is linked to Fabry disease), they are at a much greater risk of developing the condition. The Genetic Test section looks at inheritance of the disease in greater detail.

Does my ancestry affect my risk?
There is no strong evidence to link Fabry Disease with individuals of any particular ancestry.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Treatment

The main treatment for Fabry disease is enzyme replacement therapy. In addition, treatments for symptoms, such as pain or organ problems, are specific to each patient.

What are the treatments for Fabry disease?
Enzyme replacement therapy (ERT) is used to prevent symptoms of Fabry disease. If symptoms already exist - such as pain or organ problems (e.g. heart, kidney, brain, skin, ears or eyes) - treatments are specific to each patient.

ERT: Fabry disease is caused by changes in the GLA gene that prevent it from breaking-down fatty substances (globotriaosylceramide) in your cells. When it works normally, GLA makes a molecule - called an enzyme - to break down these fatty substances. Scientists are able to make this enzyme in laboratories, which can then be given to patients using intravenous (IV) infusion (also called a 'drip'). This delivers the enzyme into the bloodstream, and is usually done once every 2 weeks. Before beginning ERT, your doctor will likely test for the following:

  • Pain, and how it affects quality of life
  • Symptoms of kidney disease
  • Symptoms of heart disease
  • Symptoms that can cause stroke/aneurysm (neurovascular disease) , such as problems with nerves, arteries, veins or lymphatics
  • Digestive (gastrointestinal) symptoms, including pain, vomiting or changes in bathroom habits
  • Other symptoms, such as hearing loss and vertigo
Treating specific symptoms: Fabry disease can lead to a wide range of symptoms, and treatments for only some common xx are covered here:
  • Several medications are used to treat pain associated with Fabry disease. These include low doses of diphenylhydantoin, carbamazepine, and gabapentin.
  • ACE inhibitors and angiotensin receptor blockers are drug therapies used to treat kidney disease, especially to lower the amount of protein in the urine, which is often an issue. People with more severe kidney problems may need a hemodialysis machine to filter waste, salt and fluid from blood, or may require a kidney transplant.
  • Aspirin or clopidogrel/Plavix are drugs that may be used to prevent stroke.
  • Aspirin and lipid-lowering drugs may help control blood pressure control and reduce the risk of heart problems

Can treatments cause any problems?

  • About 1 in 100 people (1%) of patients treated with ERTs have a severe allergic reaction to the treatment
  • Drug treatments can have side-effects - diphenylhydantoin, angiotensin II receptor blockers, aspirin and clopidogrel can lead to headache, nausea, vomiting, constipation, dizziness diarrhea, and muscle cramps. Carbamazepine can also cause gum problems. Ace-inhibitors can cause low blood pressure, low white blood cell count, and kidney/liver problems.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Genetic Test

Why do a genetic test?
Genetic testing tells us who is most at risk of Fabry disease. Testing for certain genes is particularly important if they are considered to be 'medically actionable' - meaning test results can be used to improve health care. Testing for Fabry disease offers the chance of early health management.

In the embedded video, Dr. Dan Roden of Vanderbilt University discusses how genetic testing has begun to influence treatment of patients.

What is the test?
To do a genetic test, a medical professional will use your DNA to try to see if you have a change in the GLA gene linked to Fabry disease.

Many of the people who use this website are patients in hospitals who are part of the eMERGE network. These hospitals are using DNA sequencing to test patients for a number of diseases, including Fabry disease, as recommended by the American College of Medical Genetics and eMERGE network members. Test results found to be medically ‘actionable’ (meaning they can be used to in patient health care) will be returned to patients.

I am concerned whether I should be tested or not, what should I do?
The decision to be tested might be one of the most important decisions you have to make. There are many things you may want to consider. For some people, genetic testing can have positive health benefits, while others may feel a lot of stress and worry. You can read more about these issues in the Concerns & Risks section. It may help to think about testing for a while before making a decision. You may also find it helpful to discuss issues with those close to you, or with your doctor/health professional.

What will the test result mean?
This test will tell your doctor whether you have a risk gene linked to Fabry Disease. We also test for a number of other diseases, as recommended for testing by the American College of Medical Genetics and the eMERGE network. If you are found to be at risk, your doctor or genetic counselor should help you understand your health care options.

What happens if I am found to be at risk?
If you are found to be at risk for any of the diseases that we test for, a health professional at your local site will attempt to contact you as soon as possible. Once we contact you, your doctor or genetic counselor should help you understand your health care options. These may include include increased monitoring of your health, including:

  • A physical exam
  • Having regular health checks
  • Taking a detailed family history of related problems
  • Family members may also be tested for genetic risk
  • Several treatments may be recommended (see the Treatment tab above)

What happens if I am NOT found to be at risk?
If you are found NOT to be at risk for any of the diseases that we test for, you will likely NOT be contacted. However, a small number of patients may receive a medical report with results, while other patients may be re-contacted about another research study

If you have not been rec-contacted, please DO NOT ASSUME that you have been tested. There are a number of reasons testing may not have happened yet. For example, studies can sometimes take a very long time to complete, and DNA samples are often not usable because of quality-control issues.

How is the test being performed?
Testing is performed on your DNA, usually from a blood sample. For many patients, your hospital or treatment center may already have some of your DNA stored in a biobank. You may be asked for an additional sample or be asked to give us permission to do testing on the existing samples.

Will it hurt?
For some patients, we may need an additional blood sample. Taking blood may cause some pain, bleeding or bruising at the spot where the needle enters your body. Rarely, taking blood may cause fainting or infection.

Is it safe?
There is a risk that you may experience pain or bleeding if you need to give an additional blood sample. Risks concerning privacy are discussed under Concerns & Risks.

How long will I have to wait for results?
Unfortunately, we cannot give an accurate estimate for the time you will have to wait for results - this will depend on the resources available at the location where you receive treatment and were tested.

Is this a standard test?
Although increasingly more common, this test is not yet standard, and is typically offered as part of a research study.

What type of test is this?

  • Is this test intended to help make a diagnosis? Yes
  • Is this test intended to predict a family history of disease? Yes
  • Is this test intended to check if I am a carrier for a particular disease? Yes
  • Is this test intended to screen for genetic disorders? Yes
  • Is this test intended to screen for disorders related to pregnancy? No
  • Is this test intended to screen for disorders related to newborns? No

Will I need to have this test done more than once?
No, you should not need to have this test done more than once. You will need to keep track of your testing result in order to share with all of your doctors, including those you see at other medical care centers.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Family

Will my genetic test results affect my family?
Your genetic test results may affect your family. In the embedded video, Maureen Smith, a researcher at Northwestern University, recommends first discussing genetic test results with your doctor. Your doctor may refer you to a genetic counselor, who can help you understand test results and guide you toward brochures and websites that can provide information for both you and your family.

  • Before your genetic test: Because genetic information is inherited, it is important to be aware that your genetic test results are often relevant to your family members as well. Results may indicate that you are at risk, or that you are a carrier (see below). Before you have a genetic test, it can be a good idea to think about if and how you would like to share results with your family. Your doctor or genetic counselor should be able to provide more information about this.
  • After your genetic test: For many of the diseases we test for, genetic test results may be relevant to your family members, as well as to you. You may be at risk, and you may be a carrier (see below). If you already have results, it is again important to think about sharing them with family. Again, your doctor or genetic counselor should be able to offer advice on how genetic testing may affect your family members.

Can you (briefly) explain heritability?
We each have about 24,000 genes, which carry the instructions for making and maintaining our bodies. For each gene we typically have two copies – one inherited from each parent. If genetic test results suggest you are at risk of developing a heritable disease, you will have inherited the risk from one or both your parents. Your brothers, sisters, children, parents, and other relatives may also be at risk of developing the same disease.

How is Fabry disease inherited?
Fabry disease is inherited in an X-linked manner. This means it is caused by a change in the X-chromosome (where the GLA gene is located). Men have only one X-chromosome, while women have two. For this reason, the disease is usually more severe in men (women typically have one 'normal' version of GLA, on the other X-chromosome). This pattern of inheritance can mean different things for different family members - the information below is adapted from GeneReviews (Mehta and Hughes, updated 2013):

Parents of a male with Fabry disease:

  • The father of a male with Fabry disease is not affected.
  • In a family with more than one person with with Fabry disease, the mother of a male with Fabry disease carries the disease risk gene (and may/may not have symptoms).
  • If only one (male) person in the family has Fabry disease, the mother likely carries the disease risk gene (and may/may not have symptoms). It is also possible (but unlikely) that the disease is caused by a new genetic change, not inherited from mother/father.

Brothers/sisters of a male with Fabry disease:
  • The risk to brothers and sisters depends on whether the mother carries the disease risk gene (and may/may not have symptoms).
  • If the mother of a male with Fabry disease carries the disease risk gene (and has/not symptoms), the chance of transmitting it in each pregnancy is 1 in 2 (50%). Brothers children who inherit the risk gene will have Fabry disease; sisters who inherit the risk gene will also carry the disease risk gene, and may/may not have symptoms.
  • If the disease-causing risk gene cannot be detected in the DNA of the mother of the only affected male in the family, the risk to brothers and sisters is low but greater than that of the general population.

Brothers/sisters of a female with Fabry disease, or with a Fabry disease risk gene:
  • If the risk gene was inherited from her affected father, all of her sisters will be carry a risk gene (and may/may not have symptoms) and none of her brothers will be affected.
  • If the risk gene was inherited from her mother, there is a 1 in 2 (50%) chance of transmitting the GLA mutation in each pregnancy. Male brothers/sisters who inherit the risk gene will have Fabry disease; female brothers/sisters who inherit the mutation will also carry the disease risk gene (and may/may not have symptoms).
  • Even if the disease-causing risk gene has not been identified in the father's DNA, sisters of a female carrier may still be at increased risk of inheriting the disease-causing risk gene.

Children of a male with Fabry disease:
  • All daughters of a male with Fabry disease carry the risk gene, and may/not have symptoms of Fabry disease.
  • All sons of a male with Fabry disease do not have the disease

Brothers/sisters of a female with Fabry disease, or with a Fabry disease risk gene:
  • The risk of transmitting the GLA risk gene in each pregnancy is 50%.
  • Male children who inherit the risk gene will have Fabry disease; female children who inherit the risk gene will carry the risk gene, and may/not have symptoms of Fabry disease

Other family members: If a person has Fabry disease, their maternal aunts (mother's sisters) may be at risk of carrying the risk gene, and the aunts' children, depending on their gender, may be at risk of being carriers and/or of having Fabry disease. At-risk females should be offered clinical examination, genetic counseling, and molecular genetic testing. Please note that the Resources section provides links to a number of websites that provide a much more detailed explanation of inheritance! Learn.Genetics at the University of Utah have a much more detailed explanation, which we find quite good – you can check it out here.

My children are under 18 years of age – should they be tested?
The American College of Medical Genetics recommend testing children for most of the diseases listed on this website. Health management can be effective in children at risk of Fabry disease before they reach 18 years of age.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Concerns & Risks

What Should I Do If I Have Concerns About Genetic Test Results?
If you are concerned about genetic test results you have received, you should discuss your concerns with your doctor. Your doctor should be able to explain results to you, and may recommend you to a genetic counselor or another doctor that can further help you understand your results. Maureen Smith, a researcher at Northwestern University, discusses these concerns in the embedded video.

Is there a reason why I may be a specific risk?
For most of the disorders discussed on this site, the American College of Medical Genetics recommends genetic testing for individuals with available genetic data.

Are there any implications for having children?
Yes, please see the Family section

Can I expect to experience emotional consequences related to my test result?
A range of reactions are possible and normal. Some patients may experience anxiety or other negative reactions related to genetic testing and results. If this is the case, please discuss with your doctor, who can address your concerns and refer you another health professional if required.

Can I expect to experience social consequences related to my test result?
Some people may feel that there is a stigma attached to having a genetic disease. If you do experience or anticipate any negative social reactions, please discuss with your doctor who can address your concerns.

Can I expect to experience an increase in anxiety?
Many individual experience increased anxiety related to genetic testing. Again, please discuss with your doctor if this is the case.

Are there any implications in terms of discrimination arising from the test result?
Health insurance companies are prevented by law from discriminating against you based on your genetic test results. However, the same law does not apply to long-term disability insurance or to life insurance. Maureen Smith, a researcher at Northwestern University discussed these issues in the video on this page.

If I am found to be at increased risk for developing a disease, are there similar health implications for my family?
Yes, your results may have similar health implications for your family. Please see the Family section.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Sharing

Should I tell other health care providers about my test result?
We do recommend that you share this information with your health care providers. However, as explained by Maureen Smith, a researcher at Northwestern University, what you decide to do with your results is up to you.

Who will see my test results?
People who have access to your medical record will be able to see your genetic test result. This may include health professionals such as doctors, nurses, pharmacists, and genetic counselors. However, health professionals from other centers or hospitals will likely not have access to your results.

Should my other family members be tested?
If you are found to be at risk for a heritable genetic disease, your family may also be at risk. We discuss this further in the Family section.

Will this affect my health insurance?
No, your health insurance will not be affected by this test result. However, as discussed below by Maureen Smith, a researcher at Northwestern University, your life insurance and other areas of your life may be affected.

Who can I contact if they have any more questions?
You can contact your local center, where you received the test. The Resources section also includes a lot of websites that we recommend.

Is it there a risk to my privacy?
Research that uses information from medical records and that involves genetic testing can affect your privacy. Your participation in this research will be held strictly confidential, and only coded numbers will be used to identify specimens and research records. While it is impossible to absolutely guarantee that information in our secure system will never be known by others, we are taking every possible precaution to see that this does not happen.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Resources

We are compiling a list of websites to help you understand genetics and genetic test results. If you would like to suggest other resources for this section, please feel free to This email address is being protected from spambots. You need JavaScript enabled to view it.!
INFORMATION ABOUT FABRY DISEASE:

Weblink to Genetics Home ReferenceGenetics Home Reference
Extensive resource about rare and genetic and genetic diseases. The above link leads to their familial Fabry disease pages. A link to the main site is provided below as well.


Weblink to Genetic and Rare Diseases Center (GARD) - Fabry Disease ResourcesGenetic and Rare Diseases Center (GARD)
Supported by the NIH, this website has great resources for a huge range of genetic and rare diseases. The above link is to their Fabry disease resource. A link to the main GARD site is provided below as well.


Weblink to Fabry Community WebsiteFabry Community (a Genzyme-supported site)
Dedicated Fabry disease resources for both patients and healthcare professionals. Please note, this site is supported by Genzyme, which develops and markets enzyme replacement therapy for Fabry disease.


INFORMATION ABOUT GENETICS AND GENETIC TESTING:

Weblink to Genetics Home Reference Genetics Home Reference
Consumer-friendly information about the effects of genetic variations on human health. Federally-supported resources, include reviews of more than 800 genetic diseases and more than 1000 genes.


Weblink to Learning Resources from the NHGRILearning Resources from the NHGRI
Lots of very good resources from the NHGRI, including major sections about The Human Genome Project, Facts Sheets, and educational resources for teachers and students.


Weblink to National Society of Genetic CounselorsFind a Genetic Counselor
The National Society of Genetic Counselors have a searchable database of genetic counselors. Their website also includes some education materials for patients and healthcare professionals.


Weblink to NHGRI Talking GlossaryNHGRI Talking Glossary
Talking glossary of genetic terms developed by the National Human Genome Research Institute. A huge range of definitions is provided by researchers from around the world.


Weblink to Help Me Understand GeneticsHelp Me Understand Genetics
Help Me Understand Genetics is a handbook from the National Institutes of Health that contain useful information about genetics in clear language and provides links to even more online resources. The entire handbook can also be downloaded as a pdf.


Weblink to the Genetic and Rare Diseases Information CenterGenetic and Rare Diseases Information Center (GARD)
A joint project from The Office of Rare Diseases Research (ORDR) and the National Human Genome Research Institute (NHGRI) that provides searchable information about genetic conditions and rare diseases. It also includes a list of FDA-Approved drugs and other medical products for treating rare disease.


Weblink to NORDNational Organization for Rare Disorders - Resources for Parents/Families
The National Organization for Rare Disorders (NORD) is a volunteer organization dedicated to empowering the rare disease community. Again, they have some very nice web resources.


Weblink to ELSIEthical, Legal and Social Implications Research Program
The ELSI Research Program supports examinations and investigations of the ethical, legal and social implications of genetics research.


Weblink to GINAGenetic Information Nondiscrimination Act of 2008
The Genetic Information Nondiscrimination Act of 2008, also referred to as GINA, is a new federal law that protects Americans from being treated unfairly because of differences in their DNA that may affect their health.


Weblink to Learn.GeneticsLearn.Genetics, University of Utah
Excellent resources, especially for those involved in education. Includes a catalog of animations, videos, interactive features, and virtual labs.


Weblink to the Dolan DNA Learning CenterDolan DNA Leaning Center
The DNALC provides genetics learning resources for teachers and students.


INFORMATION FOR RESEARCHERS:

Weblink to the ClinVar ACMG recommendations pageClinVar: ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing
Clinvar's dedicated ACMG page - a useful jumping-off point to the Genetic Testing Registry, OMIM, MedGen, and local ClinVar pages for each gene.


Weblink to Fabry Disease GeneReviews pageGeneReviews
Mehta and Hughes. GeneReviews: Fabry Disease (updated October, 2013).


Weblink to Fabry Disease: Perspectives from 5 Years of FOSFabry Disease: Perspectives from 5 Years of FOS
Mehta, Beck, and Sunder-Plassmanne (2006).


About

What is the purpose of this information?
Our aim is to provide information about why we do genetic testing. We try to answer some common questions and offer guidance on some personal and practical issues. This information is for anybody with questions about genetic testing for any of the diseases and drugs listed in this site.

Are there geographical differences in testing, service or treatment?
Different centers have different policies in terms of how tests are administered and results shared. However, the results discussed in this document should be relevant to most individuals tested for risk of developing genetic disease.

How is this paid for?
If you received this test as part of the eMERGE research study, neither you nor your insurance company will have to pay anything toward this test

When was this content last updated?
September 19, 2016.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.
You are here: Home Results Disorders (A-J) Fabry Disease