Disorder name: Fabry disease
- What is Fabry disease?
- What causes Fabry disease?
- What are the symptoms of Fabry disease?
- What is the treatment for Fabry disease?
- What happens when Fabry disease is treated?
- What causes the alpha-galactosidase A enzyme to be absent or not working correctly?
- How is Fabry disease inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test for Fabry disease during a future pregnancy?
- Can other members of the family have Fabry disease or be carriers?
- Can other family members be tested?
- How many people have Fabry disease?
- Does Fabry disease happen more often in a certain ethnic group?
- Does Fabry disease go by any other names?
- Where can I find more information?
This fact sheet contains general information about Fabry disease. Every child is different and some of this information may not apply to your child specifically. Certain treatments may be recommended for some children but not others. If you have specific questions about Fabry disease and available treatments, you should contact your doctor.
WHAT IS FABRY DISEASE?
Fabry disease is an inherited disorder that can affect many parts of the body, especially the heart and kidneys. People with Fabry disease have problems breaking down a substance in the body called globotriaosylceramide (GL-3). Fabry disease belongs to a group of disorders known as These are a group of rare inherited disorders. People with lysosomal storage disorders have problems with breaking down large molecules within the lysosome. When the enzymes inside lysosomes are missing or not working properly, there can be a buildup of these molecules which causes a variety of health problems..
|Lysosomal Storage Disorders:
Lysosomal storage disorders (LSDs) are a group of inherited disorders. They are caused by A molecule that helps chemical reactions take place. For example, enzymes in the stomach speed up the process of breaking down food. Each enzyme can participate in many chemical reactions without changing or being used up. that do not work properly.Lysosomes are like recycling centers for The smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts.. They are small sacs filled with enzymes. These enzymes help break down large molecules into smaller molecules that the body can re-use. People with LSDs are missing enzymes or have non-working enzymes. As a result, these people have problems breaking down certain large molecules into usable forms. This leads to a buildup of these molecules, which causes a variety of problems.The symptoms and treatment vary between LSDs. They can also vary from person to person with the same LSD.
WHAT CAUSES FABRY DISEASE?
Fabry disease is caused by problems with the enzyme called alpha-galactosidase A (alpha-GAL). In people with Fabry disease, alpha-GAL is missing or not working properly. Normally, alpha-GAL helps cells break down a substance called GL-3 into smaller particles that can enter the bloodstream and eventually be discarded or reused. When alpha-GAL doesn’t function properly, GL-3 accumulates in cell Lysosomes are like recycling centers for cells. They are small sacs filled with many enzymes that help break down large molecules into smaller molecules that the body can re-use., eventually causing cell damage.
WHAT ARE THE SYMPTOMS OF FABRY DISEASE?
Fabry disease can cause problems in many systems of the body. The disease is commonly characterized by:
- Episodes of pain in the hands and feet (acroparesthesias)
- Clusters of small, dark red spots on the skin (angiokeratomas)
- Decreased ability to sweat (hypohidrosis)
- Cloudiness of the front part of the eye (corneal opacity)
- Hearing loss
Over time, people with Fabry disease can develop more severe complications such as:
- Kidney damage and kidney failure
- High blood pressure (hypertension)
- Heart disease like This is a condition that causes the heart muscle to become weak and enlarged. These changes make it more difficult for the heart to pump blood. If not treated, it can be life-threatening. Some of the causes include certain metabolic disorders, viruses, alcohol, or a heart attack.
- Heart attack
- Cerebrovascular disease (disease from abnormal blood flow to the brain), like a This is when the blood or oxygen supply to part of the brain is stopped. It can be caused either by a blood clot or a leak in a blood vessel. A stroke may cause loss of speech and language and the ability to move certain body parts. If severe, it can cause death.
WHAT IS THE TREATMENT FOR FABRY DISEASE?
People with Fabry disease should be treated by a team of specialists who are familiar with the disorder. Which specialists are needed will depend on the person’s symptoms. All people with Fabry disease should be seen by a biochemical genetics doctor (or This is a doctor or medical geneticist who has special training in diagnosing and treating metabolic disorders. They often work in university hospitals or large medical centers.). Their team may also include a A cardiologist is a doctor who specializes in the heart. (heart doctor), audiologist (hearing doctor), A specialist in the anatomy, functions, and organic disorders of nerves and the nervous system. (brain doctor), nephrologist (kidney doctor), and a These are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder.. This team can support the family and help manage the symptoms of Fabry disease.
Treatment for Fabry disease has two main goals: 1) replace or increase the function of alpha-GAL, and 2) alleviate symptoms and prevent future complications.
- A type of therapy that can be used in some metabolic disorders. In people who have certain enzymes either missing or not working correctly, an IV infusion that contains the enzyme can be given. Enzyme replacement therapy is not a cure, but can help with the health problems and symptoms of the disorder.
Fabry disease is caused by not having enough of an enzyme called alpha-GAL. Enzyme replacement therapy gives people a replacement form of that enzyme. This is a long-term treatment option, but it is not considered a cure. ERT is a lifelong treatment and is administered by intravenous infusion every other week. Some experts have recommended that ERT be started as early as possible in all males with Fabry disease and in female A person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation. that have serious symptoms. ERT may reduce the long-term risk for cardiac, cerebrovascular, and kidney complications. It may also help pain episodes.
- (Also known as Pharmacological chaperone therapy) is a new type of medicine using chaperones. Chaperones are small molecules that help enzymes become functional by helping them take the correct shape and by helping them stay stable. Increasing the function and stability of specific enzymes may help prevent or slow down some disease symptoms.
A new type of medication called a chaperone therapy can be used to restore alpha-GAL in patients with specific Relating to (or due to) genes and heredity or the field of studying genes and heredity. A variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation. causing their Fabry disease. This medication does not work for all patients with Fabry disease. Chaperones are small molecules that help enzymes become functional by correcting their shape and increasing their stability. The chaperone therapy medication attaches to certain unstable forms of alpha-GAL and stabilizes this enzyme which improves how it works in the body. This improvement in enzyme function helps stabilize kidney function and help with a specific heart issue. This therapy is approved for individuals that are 16 years of age or older.
- Pain Management
Medications including a medication used to treat and prevent seizures, a medication used to treat seizures, convulsions, nerve pain and other conditions, or a medication used to treat nerve pain and seizures may be used to treat pain in the hands and feet.
- Kidney Support
Kidney problems and high blood pressure may be treated with ACE inhibitors. If kidney damage becomes extensive, a kidney transplant may be necessary.
- Psychosocial Support
Individual and family counseling, disease education, and participation in patient organizations, advocacy groups, and support groups are important for managing the emotional and psychological impact of Fabry disease.
WHAT HAPPENS WHEN FABRY DISEASE IS TREATED?
While treatment can help alleviate symptoms and avoid some complications, Fabry disease tends to be progressive, meaning symptoms and problems get worse over time. The most common cause of death in individuals with Fabry disease is heart and blood vessel disease (cardiovascular disease). Individuals with Fabry disease should have their kidney function, heart (cardiac) function, and hearing monitored yearly and consider having brain imaging (This test uses magnetic waves to make pictures of the body. It can sometimes be used instead of x-rays to look at areas inside the body. It is often used to look at the brain or other inner organs.) every 2 years.
WHAT CAUSES THE ALPHA-GALACTOSIDASE A ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body to make different enzymes. The GLA gene provides the instructions to make alpha-GAL. Males have one copy of the GLA gene and females have two copies of the GLA gene. In males with Fabry disease, the one copy of their GLA gene does not work correctly. Females may have either one or two nonfunctioning GLA A segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases.. Because of the changes in the GAL gene, the alpha-GAL enzyme either does not work properly or is not made at all.
HOW IS FABRY DISEASE INHERITED?
Fabry disease is Acquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. in an X-linked pattern. In this type of inheritance, the gene, GLA, is located on the One of the two chromosomes that are responsible for determining the sex of an organism. The other sex chromosome is called the Y chromosome. Both the X and the Y chromosome contain several genes, only some of which are involved in determining sex. In humans, the X chromosome is the larger of the two sex chromosomes. Females usually have two X chromosomes and males usually have one X chromosome and one Y chromosome., one of the sex A strand of DNA contained within a cell. Each chromosome contains many thousands of genes. In humans, there are a total of 46 chromosomes, half of which come from each parent. The combined total of all chromosomes in a cell is the genome.. Genes usually come in pairs, with each parent giving one copy to their child. The sex chromosomes, however, are different.
A male inherits one X chromosome from his mother, and one Y chromosome from his father. A female inherits two X chromosomes, one from each parent.
A male with a non-working copy of the gene for Fabry disease on his X chromosome will have Fabry disease. This is because males do not have a second X chromosome with a working copy of the gene. Because of this, it is more common for males to have Fabry disease than females.
Females with one non-working copy of the GLA gene on one X chromosome are variably affected by Fabry disease. They may experience the same symptoms as affected males, milder symptoms than affected males, or even no symptoms at all.
If a mother has one non-working copy of the GLA gene, she is called a carrier. For carriers, there is a 50% chance that each male pregnancy will have Fabry disease. For carriers, there is a 50% chance that each female pregnancy will be a carrier, like her mother.
A father passes his One of the two sex chromosomes that is responsible for determining the sex of an organism. The other sex chromosome is called the X chromosome. Both the X and the Y chromosome contain several genes, only some of which are involved in determining sex. In humans, the Y chromosome is the smaller of the two sex chromosomes. Most females have two X chromosomes and most males have one X chromosome and one Y chromosome. to his sons and his X chromosome to his daughters. Therefore, if a father has Fabry disease, none of his sons will have the disease and all of his daughters will be carriers.
Source: OpenStax CNX
Genetic counseling is available to families who have children with Fabry disease. Genetic counselors can answer questions about how Fabry disease is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselor.
IS GENETIC TESTING AVAILABLE?
Genetic testing for Fabry disease can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes (variants) in the GLA genes that causes Fabry disease. If a gene change has been found in other family members, testing can find out if your child has the same gene change.
Deoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing is not always necessary to diagnose Fabry disease in boys. However, genetic testing is necessary to determine whether females are carriers. Genetic testing can also be used to determine if certain medications can be helpful to treat Fabry disease.
WHAT OTHER TESTING IS AVAILABLE?
The process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages. Tests
A screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder.
Newborn screening for Fabry disease is done in some states. A blood spot from the baby’s heel is used to screen for many different conditions. Newborn screening detects Fabry disease by looking for alpha-GAL enzyme activity. Alpha-GAL enzymes are active in every healthy newborn’s blood. Since babies with Fabry disease have alpha-GAL enzymes that are either missing or not working properly, they will have reduced alpha-GAL enzyme activity.
If a baby has a positive result on the initial Fabry newborn screen, it does not always mean that he or she has Fabry disease. Low alpha-GAL enzyme activity levels can sometimes be found in people who never develop Fabry disease. A positive screening result means that further testing must be done to confirm or rule out Fabry disease. Rarely, there can also be false positives with additional testing.
For males, the amount of alpha-GAL enzyme activity is measured in the blood or in other cells from the body. In females, DNA testing is necessary to confirm the diagnosis as some female carriers have normal alpha-GAL levels in their blood.
Genetic testing of the GLA gene may also be performed to help confirm the diagnosis.
CAN YOU TEST FOR FABRY DISEASE DURING A FUTURE PREGNANCY?
If a genetic cause has been identified, DNA from the fetus can be tested. The sample for this testing is obtained by either CVS or This is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy..
Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have Fabry disease. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE FABRY DISEASE OR BE CARRIERS?
Only some states offer newborn screening for Fabry disease. It is very important that other family members are told that they could be at risk of having Fabry disease or being carriers.
Having Fabry disease
Each full brother (same mother and father) of a baby with Fabry disease has a 50% (1 in 2) chance of also having Fabry disease. Even older siblings who have not shown any symptoms of the disease could have late-onset Fabry disease that has not caused symptoms yet, but will in the future. All siblings of an individual with Fabry disease should be tested to see if they also have Fabry disease because early treatment can prevent more serious health problems.
In addition, the father of a female baby who is found to be a carrier of Fabry disease after newborn screening could also have Fabry disease and not yet noticed or experienced any symptoms. It is important for both parents of a female carrier of Fabry disease to be tested.
Carrier for Fabry disease
Since males cannot be carriers, unaffected brothers cannot be carriers for the disease. Sisters who do not show symptoms of Fabry disease still have a chance of being carriers like their mother. Each sister has a 50% chance of being a carrier.
CAN OTHER FAMILY MEMBERS BE TESTED?
Brothers of a child with Fabry disease should be tested, by measuring alpha-GAL enzyme activity or DNA testing to determine if they also have Fabry disease. Talk to your doctor or genetic counselor if you have questions about testing for Fabry disease.
Female family members can have DNA testing to see if they are carriers. If you have questions about carrier testing, ask your genetic counselor or doctor.
HOW MANY PEOPLE HAVE FABRY DISEASE?
It is estimated that 1 in every 50,000 males will be born with Fabry disease, although some recent studies show it may be more common than previously thought. The disease is much less common in females.
DOES FABRY DISEASE HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
Fabry disease occurs in people of all ethnic groups around the world.
DOES FABRY DISEASE GO BY ANY OTHER NAMES?
Fabry disease is also sometimes called:
- Angiokeratoma, diffuse
- Anderson-Fabry disease
- Something that is passed on from a parent to the child, usually through the genes. dystopic lipidosis
WHERE CAN I FIND MORE INFORMATION?
Fabry Support & Information Group
National Fabry Disease Foundation
National Kidney Foundation
National Institute of Neurological Disorders
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||March 30, 2018
June 1, 2020
March 16, 2023
|Update on:||March 16, 2023|
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