How Is Fabry Disease Treated?

Fabry disease is a rare, inherited condition caused by a mutation in the GLA gene. This gene is found on the X chromosome. The GLA gene controls the alpha-galactosidase A (alpha-Gal A) enzyme. This enzyme helps the body break down a certain type of fat called GL-3, GB-3, or globotriaosylceramide.¹

People with Fabry disease don't make enough alpha-Gal A enzyme, so GL-3 fat builds up in cells all over the body. The fat most often accumulates around blood vessels, the heart, kidneys, and nerves throughout the body. This leads to a wide range of symptoms that can be mild to severe and even life-threatening. Symptoms include:^2-5

• Nerve pain, numbness, and tingling
• Pain attacks and overall body aches
• Fevers
• Chronic fatigue
• Problems sweating
• Swelling caused by fluid build-up (edema)
• Vision issues
• Kidney disease
• Heart disease and stroke
• Gut problems (nausea, vomiting, diarrhea, or constipation)
• Breathing problems
• Infections
• Depression
• Skin problems
• Hearing loss or ringing in the ears
• Vertigo, weakness, or lightheadedness

Some symptoms begin in childhood. For example, signs of nerve pain such as sharp, burning pain in the hands and feet, especially during exercise, is a common first symptom. Fabry disease is a progressive disease, meaning it gets worse over time. There is no cure, but there are treatments that help some people.^1,2,5

Fabry types

Type 1 is classic Fabry disease. Type 2 is later-onset or nonclassic Fabry disease. Both types can lead to kidney failure, heart disease, and shortened lifespan.⁴

Men with type 1 classic Fabry generally have more severe symptoms because they have little to no functional alpha-Gal A enzymes. These men tend to develop major symptoms as children and teens, especially pain, and may live to about 50 years old.^4,5

Men with type 2 later-onset have a little alpha-Gal A enzyme in their body. This allows them to feel and appear healthy in their childhood and teen years. However, symptoms become noticeable in these men sometime between their 30s and 70s.⁴

Women with type 1 tend to have fewer and less severe symptoms than men with type 1. Some of these women have no symptoms at all. However, some women with type 1 have symptoms just as severe as men with type 1 have.⁴

How is Fabry disease treated?

Because Fabry disease may impact almost every system in the body, treatment requires many different approaches. Generally, doctors want to begin treatment as soon as possible to prevent organ damage and reduce pain. However, treatment guidelines vary widely in different countries. In the United States, there are 3 medicines approved for Fabry disease:^2-4

Agalsidase beta and pegunigalsidase alfa-iwxj are enzyme replacement therapies. This means they work by replacing the missing α-galactosidase A (alphaα-Gal A enzyme).^2,5-7

Migalastat is called a chaperone therapy because it binds to the alpha-Gal A enzyme. This enzyme is defective in people with Fabry disease. Migalastat stabilizes the protein and allows it to travel to and break down certain fats.^2,5,6

Pegunigalsidase alfa-iwxj has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because it can cause hypersensitivity reactions, including anaphylaxis.⁷

Not all of these treatments work for all types of Fabry disease.

Because each person with Fabry disease has a unique combination of symptoms and complications, there is no one-size-fits-all treatment plan.

For example, people with kidney and heart problems receive standard treatments for those conditions. Nerve pain (neuropathic pain) may be treated with certain antidepressants, anticonvulsants, and – less often – narcotics.⁵

Gut problems are treated in many ways, including with:⁸

• Metoclopramide (intestine stimulant)
• Lipisorb® (nutritional supplement)
• Pancrelipase (enzymes)

Depression and anxiety are common in people with Fabry disease, often due to the severe, chronic pain the condition can cause. Keeping a pain diary can help your doctor understand how severely pain affects your life. Counseling and behavioral modification therapy are recommended to help manage pain and depression more effectively.⁵

Lifestyle changes may also help manage some symptoms. Extra stress, overdoing it physically or mentally, and temperature changes should be avoided because these can trigger a pain crisis. Eating smaller, more frequent, low-fat meals can help manage gut issues.⁵

Research is underway to find more effective treatments for Fabry disease.