Rare Disease

Fabry Disease

  
Section I

What is Fabry Disease?

Fabry disease is the absence or deficiency of the lysosomal enzyme, α-galactosidase A. The function of α-Gal A is to break down glycolipids. Without it, sugars and fatty acids (specifically GL3) accumulate in the lysosomes. When these start to accumulate, it results in cell abnormalities and impairs several major organs' function. This accumulation can cause tiny blood vessels to clog, affecting the organs that depend on these blood vessels, including the heart, kidneys, skin, inner ear, and nervous system. (NORDCanadian Fabry AssociationGARD)

Why is Fabry considered a Rare Disease?

rare disease is a disease that affects only a small percentage of the population. Other rare diseases include Pompe disease, Gaucher disease, Mitochondrial disease, and many more. Fabry is a rare disease diagnosed in males at an estimated 1 in 40,000 to 60,000 people. Since females can be asymptomatic, the number of women affected by Fabry disease is unknown. (NORDCanadian Fabry AssociationFabry Disease NewsRare Disease Day)

Fabry is a rare disease caused by a defective gene in the X-chromosome, meaning it is an inherited disorder. A family member being diagnosed with Fabry disease can lead to another relative also being evaluated and diagnosed. (Fabry International NetworkNORD)

Learn more about the inheritance of Fabry here.

  
Section II

Signs and Characteristics

There are many signs and characteristics that may show up when an individual has inherited Fabry disease. These can help to predict whether someone should see a Fabry specialist. Since each individual is different, the signs and characteristics that they experience can differ from other individuals. Some signs and characteristics that an individual may see include:

Pain

Pain is experienced as either constant pain in the hands and feet (known as acroparesthesia) or as sharp pains that run throughout the body (also known as "Fabry Crisis"). Episodes of increased pain can be caused by GL3 build-up, extreme humidity, high temperature, exercise, stress, and fatigue. (Canadian Fabry AssociationNORD)

Heart

An irregular or racing heartbeat may be a sign that the heart is affected due to an accumulation of GL3, leading to circulatory issues. An increased or irregular heartbeat can lead to high blood pressure, enlarged heart, heart attacks, mitral valve prolapses, arrhythmia, stroke, or heart failure. (Canadian Fabry Association)

Kidneys

When GL3 accumulates, the function of the kidneys reduces over time and can lead to kidney failure. A sign to watch out for is protein in the urine, which can be found through a urine sample. GL3 in the kidneys prevents the kidney from filtering correctly. (Canadian Fabry Association)

Skin rash

A spotted rash that is reddish to dark-blue in colour and usually found between the stomach and the knees is the most visible sign of Fabry. (NORD)

Impaired ability to sweat

When GL3 accumulates in the sweat glands, it causes people to sweat very little, if at all. This can lead to symptoms similar to a fever due to the body overheating and heat sensitivity. (Fabry International Network; NORD)

Other signs and symptoms can include:

  • Change in hearing: experiencing tinnitus, ringing, or hearing loss
  • Corneal opacity: hazy or opaque cornea in the eye (does not impact vision)
  • Gastrointestinal problems: pain, diarrhea, nausea, or bloating after meals
  • Neurological: headaches and vertigo
  • Other signs: leg swelling, shortness of breath, osteoporosis, and delayed puberty

To find out more about Fabry disease symptoms, visit Canadian Fabry Association or NORD.

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Section III

Who is at risk for Fabry Disease?

When discussing diagnosis, it's essential to understand who is at risk of developing Fabry disease. Fabry is an inherited disorder where the defective GLA gene is on the X-chromosome, one of the two chromosomes that determines a persons sex. (Canadian Fabry Association)

Chromosomes carry the genetic information of each individual. Organized in pairs, the 23rd pair of human chromosomes determine sex. Females have two X-chromosomes, and males have one X-chromosome and one Y-chromosome. In X-linked disorders, the disease symptoms can be masked in females by the other X-chromosome that is not affected. (NORD)

Everyone inherits their chromosomes from their parents. Chromosomes are formed in pairs, where one chromosome comes from each parent so that everyone's genetics come half from their mother and half from their father. For this reason, if a mother (two X-chromosomes) carries the Fabry gene, her children, regardless of sex, will have a 50% chance of inheriting the Fabry gene. If a father (one Y-chromosome and one X-chromosome) carries the gene, 100% of his female children will inherit the Fabry gene, and 0% of the male children will inherit the Fabry gene. This is because each child inherits an X-chromosome from their mother and either an X-chromosome or a Y-chromosome from their father. (Canadian Fabry AssociationNORD)

Fabry can occur in both women and men and occurs across all racial and ethnic populations. Males will often be affected severely by the symptoms, and for females, it's more varied as they can be seemingly asymptomatic, have severe symptoms, or anything in between the two. (GARDNORD)

  
Section IV

Diagnosis

Receiving an early diagnosis may be crucial for beginning to manage the signs and characteristics that present themselves, reduce the risk of problems getting worse, and help other family members receive a diagnosis. Fabry is a rare disease and can often be hard to diagnose. It shares signs and symptoms with other conditions such as multiple sclerosis, arthritis, Crohn's disease and many more. (Canadian Fabry AssociationFabry International Network)

Health care providers will often look at family history, symptoms, physical exams and do a laboratory test before making a diagnosis. Fabry testing is usually done through a laboratory test (an enzyme assay) which measures the amount of alpha-GAL enzyme activity within the blood. This type of testing is more reliable for males than females. (GARD; Cleveland Clinic; Fabry International Network)

For women, genetic testing (DNA sequencing) is more accurate for diagnosing Fabry. This is because women with Fabry disease may have normal levels of alpha-GAL enzymes, which will cause a normal test result when doing an enzyme assay. (Cleveland Clinic; Canadian Fabry Association)

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There are also newborn screening tests for Fabry. This is especially important for parents who carry the gene as they can pass it on to their children. (GARD; Cleveland Clinic)

If you're at risk or have a family member with Fabry, reach out to a Fabry specialist about getting tested for Fabry.

  
Section V

Treatment

At present, there is no cure for Fabry disease. However, there are treatments that can aid in managing the signs and characteristics of Fabry and improve an individual's life quality. A specific treatment plan should be set in place by a health care provider that specializes in Fabry disease, as each individual will present differently.

Enzyme Replacement Therapy (ERT)

This medical treatment replaces the deficient or absent enzyme and reduces the accumulated glycolipids in cells. For Fabry disease, this means replacing the α‐galactosidase A (α‐Gal A) enzyme. This therapy increases the concentration of the α‐Gal A enzyme. This therapy requires patients to come in biweekly throughout their lives for frequent infusions of the enzyme. In Canada, there are two ERT drugs approved by Health Canada: agalsidase alpha (Replagal®) and agalsidase beta (Fabrazyme®). ERT in Canada was approved for Fabry treatment in 2004. (Canadian Fabry AssociationNORDCleveland Clinic)

Oral Chaperone Therapy

Small molecules that repair the alpha-GAL enzyme when it is faulty are known as chaperones. Once the enzyme mends, it can break down fatty substances. This therapy requires individuals to take a pill (migalastat [Galafold®]) every day to stabilize the faulty enzyme. This pill works by binding to, stabilizing, and enhancing the activity of the enzyme. This treatment may be recommended based on the specific genetic mutation in the GLA gene. (NORDGARD; Cleveland Clinic)

Other Emerging Therapies

Substrate Reduction Therapy (SRT): This therapy uses an oral drug to help stop the synthesis/production of substrate that accumulates by not being degraded and stored. (Canadian Fabry Association)

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Gene therapy: this therapy introduces healthy genetic material into the cells of a person to help fight disease by getting to the source. This therapy is still being researched and undergoing trials. (Fabry International NetworkCanadian Fabry Association)

    
Section VI

Living with Fabry Disease

Fabry disease can cause an array of signs and characteristics that impact an individuals quality of their life. It can be challenging to be diagnosed with a rare disease, which causes the mental and physical health of a person to be worn down. However, there are actions and steps that can help improve the quality of life for people who are living with Fabry disease.

  • When living with a rare disease, it's beneficial to have a support network - this can be friends, other Fabry patients, or family that help navigate and provide emotional support. It can assist mental wellness to have individuals who can give support when it's needed. (National Institute of Mental Health)

  • Following medical treatments prescribed by health care practitioners can help with symptom management, such as alleviating symptoms that cause pain. (Fabry Disease News)

  • It's normal to feel stressed when being diagnosed with a medical condition. It can cause uncertainty about the future, financial strain, the feeling of isolation, and symptom discomfort. One way to obtain stress relief can be by having open communication with both loved ones and a care team about how you're feeling. (Fabry Disease News)
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  • Take advantage of the community resources that are available to individuals living with a medical condition. There are government services available to make your life easier and help you in your daily life, including therapy programs. (National Institute of Mental Health)
  • Stay up to date on Fabry news and clinical trials that are happening. As awareness becomes raised for Fabry disease, there may be more options that become available for the management of Fabry disease. (Fabry International Network)
Section VII

Resources

We've complied a list of resources to help you get started on your journey 

Find clinical trials for Fabry: 

Canadian Fabry Association: 

To learn more about gene therapy: Fabry International Network

Blog about living with Fabry disease: Fabry Disease News

Read a story from Marlou, an individual with Fabry: Amicus Theraputics

Contributor:

Alexa Headshot

Alexa Smith

Topic Specialist

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