What Is Fabry Disease?

Fabry disease is a rare genetic lysosomal storage disorder that mainly affects the heart, nervous system, and kidneys, often leading to life-threatening symptoms. While the disease occurs in both sexes, males are generally more severely affected than females, who may live their entire lives without any signs of disease.

It is estimated that the classic, more severe type of Fabry disease, which usually develops in childhood or adolescence, affects 1 in 22,000–40,000 males, while its later-onset, somewhat less severe (atypical) form affects about 1 in 1,000–3,000 males and 1 in 6,000–40,000 females. The frequency of classic disease in females is currently unknown.

Children with Fabry disease often live into adulthood and can have a good quality of life with proper care, but they will likely have a 10- to 20-year shorter life expectancy than people without the disease.


Fabry disease is caused by mutations in the GLA gene, which is located in the X chromosome (one of the two sex chromosomes, the other being the Y chromosome). This gene provides the instructions to produce the alpha-galactosidase A (Gal A) enzyme, which is responsible for breaking down fatty molecules, mainly globotriaosylceramide (Gb3 or Gl-3), into building blocks that cells can use.

GLA mutations result in absent or markedly deficient Gal A enzyme activity, leading to the toxic buildup of these fatty molecules in small blood vessels and most tissues of the body, causing tissue and organ damage. An enzyme unable to function or with very low activity is associated with the development of the classic type of Fabry disease, while residual activity is linked to the late-onset form.

To develop the disease, a child has to inherit only one mutated copy of the GLA gene. Since males have only one X chromosome (inherited from the mother), those who inherit the mutated gene will have more severe disease. In turn, the typical presence of a healthy GLA gene copy in females — who have two X chromosomes, one from the mother and one from the father — can partly compensate for the mutated copy.

Most of these female patients will have a 50% chance of transmitting the mutated gene, and thereby the disease, to each of their children, regardless of sex. In contrast, all of the daughters of a man with Fabry disease will inherit the GLA mutation, while none of his sons will, since boys receive a Y chromosome from their fathers, instead of an X chromosome.


Symptoms of Fabry disease, which are generally more severe in males, can appear in childhood or adolescence (classic Fabry) or in adulthood (late-onset), the latter of which is usually milder in severity.

Common symptoms include episodes of severe pain, and burning and tingling sensations in the hands and feet — which may be triggered by exercise, fever, fatigue, and stress — and clusters of small, dark spots in several locations on the skin that become larger and more abundant with age.

Reduced ability to sweat, cloudy-looking eyes that typically do not affect vision, and hearing problems, such as ringing in the ears and hearing loss, are also frequent. Many patients experience gastrointestinal symptoms, such as diarrhea, abdominal cramping, feeling full earlier than normal, reduced appetite, nausea, and/or vomiting.

Fabry disease is also associated with kidney and heart damage, which worsens over time, potentially becoming life-threatening. Among people with the late-onset form, these types of problems are usually detected in adulthood, around age 40, and may not occur at all in women. Likely due to heart disease, respiratory symptoms, such as shortness of breath, wheezing, and dry cough, can develop.

Patients, particularly those with classic Fabry, have an increased risk of stroke.

Other symptoms can include delayed puberty, malformations of the joints and fingers, impaired hair growth, generalized weakness, chronic fatigue, and headache.


In male patients, the most common test to confirm a Fabry diagnosis is an enzyme assay that measures the activity of Gal A in the blood, which indicates the presence of the disease if it is lower than normal. Given that female patients may have Gal A activity within the normal range, this test does not provide an accurate diagnosis, and genetic testing should be performed.

In fact, genetic testing, which identifies disease-causing mutations in the GLA gene, is the only conclusive way to diagnose Fabry disease, and is recommended for any individual with a confirmed or suspected clinical diagnosis, or a history of the condition in the family.

Enzyme and genetic testing can be done before birth to see if a developing baby has a disease-causing GLA mutation. Newborn screening, through a Gal A activity test, is available in some U.S. states and other countries.


While there is currently no cure for Fabry disease, treatments are available to help manage and reduce symptoms. Given the progressive nature of the disease, early intervention is important.

The mainstay of Fabry treatment is enzyme replacement therapy (ERT), which delivers a functional, lab-made Gal A enzyme directly into the bloodstream, preventing organ damage in patients and improving their quality of life.

Currently, two main ERTs are available on the market: Sanofi Genzyme’s Fabrazyme (agalsidase beta), approved in the U.S., Canada, and Europe; and Takeda’s Replagal (agalsidase alpha), approved in several countries, including Canada, Russia, the U.K., Mexico, Israel, and many members of the European Union, but it’s not approved in the U.S. Both are administered every other week, but they deliver slightly different forms of the Gal A enzyme to patients.

Certain Fabry patients may be treated with Amicus Therapeutics’ Galafold (migalastat), an oral chaperone therapy that restores the activity of certain faulty forms of Gal A. About 35%–50% of all Fabry patients are estimated to carry GLA mutations amenable to Galafold treatment.

Painkillers and other medications to manage nerve-related pain can also be used.

Heart and anti-clotting medications may be used along with pacemakers to prevent heart attacks. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are medications used to prevent heart failure and kidney disease, and dialysis and kidney transplant may be necessary for patients whose disease has progressed to kidney failure.

Special diets low in fat and salt may be considered because they can reduce the intensity of some symptoms.


Last updated: June 7, 2021

