ESPAÑOL

Start typing and press Enter to search

ESPAÑOL

Start typing and press Enter to search

ESPAÑOL

Start typing and press Enter to search

Fabry Disease
Home
/
Fabry Disease
‹ Return to Disorder Directory

Fabry Disease Disorder Directory Child Neurology Foundation

Authors: Margaret Means, MD; Sonika Agarwal, MBBS, MD 

Children’s Hospital of Philadelphia 

Reviewed: January 2022 

JUMP TO

SUMMARY

Fabry disease is a genetic condition in which a person has trouble breaking down fatty substances called sphingolipids. People with Fabry disease have a genetic change that does not allow their bodies to make enough of a particular enzyme necessary to break down the sphingolipids. This leads to a buildup of sphingolipids in the body and can cause problems with various body functions.  

Fabry disease is considered a lysosomal storage disease. Lysosomes are parts of human cells that help break down and recycle materials. When lysosomes don’t function well, materials build up in the body and cause problems.  

Symptoms of Fabry disease can be mild or severe. They can begin anytime from childhood to adulthood. 

Symptoms can include: 

  • Pain in the hands and feet 
  • Swelling of the hands and feet 
  • Pain during physical activity 
  • Flu-like symptoms 
  • Rash 
  • Gastrointestinal issues 
  • Kidney problems 
  • Heart problems 

Males are usually affected more severely than females.  

Diagnosis is made with: 

  • Blood tests 
  • Genetic tests 

Treatment usually includes: 

  • Managing the symptoms 
  • Preventing complications 
  • Replacing the missing enzyme 
Fabry Disease 1

Disorder Overview

DESCRIPTION 

Fabry disease is a genetic condition. In Fabry disease, a person doesn’t make enough of a lysosomal enzyme called alpha-galactosidase (alpha-GAL). Enzymes help with chemical processes in the body. The alpha-GAL enzyme in particular breaks down a fatty substance called globotriaosylceramide (GB-3), a type of sphingolipid. When the alpha-GAL enzyme is not working properly, GB-3 builds up in the body. It can cause symptoms in many different organs.

There are two main types of Fabry disease:

The classic type

In the classic type, symptoms appear during childhood or adolescence. They progressively get worse over time. 

Share on social media:

The atypical (or late onset) type

In the late onset type, people may not have noticeable symptoms until adulthood. Sometimes, the symptoms are vague and mild. There is often a delay in diagnosis. The symptoms may be misunderstood as symptoms of another disorder or condition.

Share on social media:

Fabry disease is inherited in an X-linked pattern. This means that the defective, or changed, gene (the GLA gene) is on the X chromosome.  

Females have two X chromosomes and therefore have two copies of the GLA gene. As long as one gene copy is normal, females will still usually produce enough of the alpha-GAL enzyme. They may have no symptoms or less-severe symptoms.  

Males have one X chromosome and one Y chromosome. Therefore, they have only one copy of the GLA gene. In males, one abnormal variant of the GLA gene is enough to cause symptoms of Fabry disease. For this reason, males are affected much more frequently than females: 

  • About 1 in every 40,000 males has classic Fabry disease 
  • About 1 in every 1,500 to 4,000 males has atypical Fabry disease 

Females can be carriers of Fabry disease. When a female with one abnormal GLA gene variant has children, each child has a 50% chance of inheriting the abnormal variant. 

Spinal Muscular Atrophy 2

SIGNS AND SYMPTOMS 

Fabry disease can cause signs and symptoms in many different parts of the body. Males tend to have more severe symptoms. Symptoms can begin in childhood. However, they also may not appear until later in life.  

List of Symptoms of Fabry Disease 

General

  • Fatigue 
  • Flu-like symptoms 
  • Hot or cold intolerance 
  • Sweating less or not at all 
  • Pain during physical activity 
  • Dizziness 
Share on social media:

Extremities (the hands and feet)

  • Pain, numbness, or tingling in the hands and feet (acroparesthesias) 
  • Swelling in the hands and feet 
Share on social media:

Eyes

  • Changes in the clear, protective outer layer of the eye (the cornea)  
Share on social media:

Gastrointestinal

  • Diarrhea 
  • Constipation 
  • Abdominal pain 
Share on social media:

Skin

  • Raised red or purple spots on the skin (angiokeratomas) 
Share on social media:

Kidneys

  • Kidney damage 
Share on social media:

Heart

  • Heart attack 
  • Heart failure 
Share on social media:

Brain

  • Stroke 
  • Changes or abnormalities of the white matter 
Share on social media:

CAUSES

Fabry disease is caused by a change in the GLA gene on the X chromosome. The GLA gene provides instructions for the body to make the alpha-GAL enzyme. When there is a change present in the GLA gene, the enzyme may not work correctly.  

The alpha-GAL enzyme’s job is to break down the fatty substance GB-3. When it doesn’t work correctly, GB-3 builds up in the body and causes symptoms in many different organs. 

This genetic change may be inherited from a parent, or it may be a new random change in the patient.  

LAB INVESTIGATIONS

The following tests help with diagnosing Fabry disease: 

Alpha-GAL enzyme activity test

This is usually done through a blood test.

Share on social media:

Genetic test

This can look for any changes in the GLA gene. 

Share on social media:

Depending on a patient’s symptoms, other lab tests or imaging studies may be needed. These can check the function of organs such as the: 

  • Heart 
  • Kidneys 
  • Nervous system 

TREATMENT

Treatment for Fabry disease involves three primary parts: 

  1. Treating symptoms 
  2. Preventing complications 
  3. Treating the underlying enzyme deficiency 

Treating Symptoms

Treating symptoms often includes the use of medications. They can help with: 

  • Pain 
  • Vertigo 
  • Diarrhea or constipation 
Share on social media:

Preventing Complications

Medications can also help with preventing complications. For instance, they can help with: 

  • Heart function 
  • Stroke prevention 
  • Kidney function 
Share on social media:

Treating the Underlying Cause

Treating the underlying enzyme deficiency is required to manage the symptoms of this disease. This can include: 

  • Enzyme replacement therapy. This is usually given via IV infusion. 
  • Chaperone therapy. Chaperones are small molecules that help proteins function better. They act by changing the shape and stability of the proteins in the cells. This type of treatment can improve enzyme function for people with specific genetic mutations such as in Fabry disease. It is given via oral capsules. 

Some new treatments for helping with the underlying deficiency are still under investigation. They include: 

  • Gene therapy.  
  • Substrate reduction therapy. This is aimed at decreasing the toxic buildup of sphingolipids.  
Share on social media:

OUTLOOK

Most untreated patients will develop symptoms starting in childhood or young adulthood. However, some may start showing symptoms earlier or later.  

Without treatment, damage to organ systems (such as the kidneys, heart, and brain) can occur. This damage can lead to decreased life expectancy.  

  • Life expectancy of untreated males is around 50 years of age 
  • Life expectancy of untreated females around 70 years of age 

With treatment: 

  • Quality of life can be improved 
  • Complications can be reduced 
Fabry Disease

Resources 

AllStripes 
The mission of AllStripes is to unlock new treatments for people affected by rare disease. Serving as a research platform dedicated to rare diseases, AllStripes makes it easy for patients to contribute to new treatment research from home. There is no cost for patients, families, or advocacy organizations to participate, join research programs, or use the platform. AllStripes does the work to collect and analyze de-identified medical records to help power faster, better drug development. By bringing patients, doctors, and researchers together everyone learns from each other’s experiences to effectively push for better treatments across all rare conditions. They have over 40 active rare disease programs, which includes Fabry disease, and they are adding more every month.  

AllStripes partners with rare disease patient advocacy organizations and key opinion leaders to build the programs. Expert researchers produce original research insights and publications, as well as partner with academic institutions and pharmaceutical companies to make progress towards new treatments. 

Disclaimer: AllStripes is a Public Benefit Corporation funded by private investors. Child Neurology Foundation does not specifically endorse products provided by AllStripes. 

Fabry Support & Information Group 
The mission of the Fabry Support & Information Group (FSIG) is to raise awareness of Fabry disease and its symptoms, to advocate for community needs and to lead the fight for the most effective treatment possible and eventually a cure. FSIG provides a link for the Fabry community to information, each other, the medical community, researchers, the pharmaceutical industry, and regulatory authorities. FSIG strives to support affected families and individuals lead fuller lives.  

FSIG supports a Testing for Tots initiative to help fund research and encourage Fabry screening for every newborn in the U.S. Currently, Fabry disease is not on the Recommended Uniform Screening Panel list.  

Fabry International Network 
Fabry International Network (FIN) is as an umbrella organization that represents over 54 countries and 62 patient associations around the world. Membership is free and open to any national patient organization in which Fabry patients are represented. The mission of FIN is to be a global, independent network of Fabry patient associations whose purpose is to collaborate, communicate, and promote best practice to support those affected by Fabry disease. FIN participates in Fabry Awareness Month, has a young adult community (age 16 to 35), hosts webinars, and awards a yearly grant to patient led associations who educate, raise awareness, and help bring patients together. 

Childhood Stroke 1

Child Neurology Foundation (CNF) solicits resources from the community to be included on this webpage through an application process. CNF reserves the right to remove entities at any time if information is deemed inappropriate or inconsistent with the mission, vision, and values of CNF. 

Research 

ClinicalTrials.gov for Fabry Disease are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently.  

ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.   

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits.  

Find Clinical Trials For Fabry Disease

Family Stories

The Fabry Support and Information Group shares advice from adults who have been living with Fabry disease on the Patient Stories page. Encouraging words for families and kids about the symptoms and setting goals.   

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

References

Swaiman KF. In: Swaiman’s pediatric neurology: Principles and practice. Edinburgh: Elsevier; 2018. p. 326. 

Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, Bultas J, Lee P, Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR. Fabry disease: Guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006 Sep;8(9):539-48. https://10.1097/01.gim.0000237866.70357.c6. PMID: 16980809.  

Germain DP. Fabry disease. Orphanet J Rare Dis. 2010 Nov 22;5:30. https://doi.org/10.1186/1750-1172-5-30. PMID: 21092187; PMCID: PMC3009617. 

What Is Fabry Disease? [Internet]. National Fabry Disease Foundation; [cited 2021 Dec 2]. Available from: https://www.fabrydisease.org/index.php/about-fabry-disease/what-is-fabry-disease 

Fabry disease [Internet.] Genetic and Rare Diseases Information Center (GARD) – A National Center for Advancing Translational Sciences program; [cited 2021 Dec 2]. Available from: https://rarediseases.info.nih.gov/diseases/6400/fabry-disease  

Share on social media:

Start typing and press Enter to search

View more
Shopping Cart