Fabry Disease: The Complete Guide to Symptoms, Causes, Treatment and Prevention
Updated: 2 days ago
Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: November 2026
Quick Answer
Fabry disease is a rare inherited condition in which a mutated GLA gene prevents the body from making enough alpha-galactosidase A, the enzyme that breaks down sphingolipids. These fats build up in blood vessels and tissues, raising the risk of heart attack, stroke and kidney failure. There is no cure, but enzyme replacement and oral chaperone therapy can slow buildup.
What the research says
The oral chaperone migalastat helps people whose mutation it can target. In a phase 3 randomized trial of 67 patients, the primary kidney-biopsy endpoint did not differ significantly between migalastat and placebo (41% versus 28% responders, P=0.30). Among patients whose mutant enzyme was suitable for the drug and who took it for up to 24 months, kidney function stayed stable (annualized estimated GFR change of −0.30 mL/min/1.73 m²), left-ventricular mass index fell by 7.7 g/m², and the severity of diarrhea, reflux and indigestion decreased (PubMed: Germain et al., N Engl J Med, 2016 [1]).
What Is Fabry Disease? An Overview
Fabry disease is a rare genetic condition in which you do not produce enough healthy versions of an enzyme called alpha-galactosidase A (alpha-GAL). This enzyme breaks down sphingolipids, a fat-like substance, and prevents them from collecting in your blood vessels and tissues. Fabry disease is a type of lysosomal storage disorder [1].
Without functioning alpha-GAL enzymes, harmful levels of sphingolipids build up in your blood vessels and tissues. Fabry disease affects your heart, kidneys, brain, central nervous system and skin.
Key Point | What It Means |
|---|---|
Definition | A rare genetic lysosomal storage disorder |
Root cause | Mutated GLA gene on the X chromosome |
Missing enzyme | Alpha-galactosidase A (alpha-GAL) |
What builds up | Sphingolipids (fat-like substances) |
Other names | Anderson-Fabry disease, Fabry's disease, alpha-galactosidase-A deficiency |
Organs affected | Heart, kidneys, brain, central nervous system, skin |
Cure? | No — but two therapies can slow fat buildup |
The disease is also known by other names — Anderson-Fabry disease, Fabry's disease and alpha-galactosidase-A deficiency.
Types of Fabry Disease
The types of Fabry disease reflect the age when symptoms first appear.
Type | When Symptoms Begin | Key Features |
|---|---|---|
Classic Fabry disease | Childhood or teenage years | A painful burning sensation in the hands and feet may appear as early as age 2; symptoms worsen progressively over time |
Late-onset (atypical) Fabry disease | 30s or older | The first indication of a problem may be kidney failure or heart disease |
How Common Is Fabry Disease?
Approximately 1 out of every 40,000 men have classic Fabry disease. Late-onset or atypical Fabry disease is more common — it affects about 1 in every 1,500 to 4,000 men.
Experts are not sure how many women have Fabry disease. Some women have no symptoms or only mild, easy-to-dismiss symptoms, so the condition frequently goes undiagnosed.
Form | Prevalence |
|---|---|
Classic Fabry disease | About 1 in 40,000 men |
Late-onset/atypical Fabry disease | About 1 in 1,500 to 4,000 men |
Women | Unknown — frequently undiagnosed due to absent or mild symptoms |
Who Might Get Fabry Disease?
People with Fabry disease inherit a mutated gene on their X chromosome from a biological parent [1]. The mutated gene is called the GLA gene. Men inherit one X chromosome from their mother. Women have two X chromosomes, one from each parent.
A parent can pass on the faulty gene that causes Fabry disease to a child in different ways.
Parent With Fabry Disease | Inheritance Pattern |
|---|---|
Father | Passes the affected X chromosome to all daughters (100% of daughters carry the mutation); sons are not at risk because males receive the Y chromosome from their father |
Mother | 50% chance of passing the affected X chromosome to each daughter or son; some family members can carry the mutation while others do not |
Symptoms of Fabry Disease
Fabry disease symptoms vary depending on the type. Some symptoms are mild and might not appear until later in life. Men tend to have more severe Fabry disease symptoms than women.
Symptom | What It Involves |
|---|---|
Numbness, tingling, burning or pain | In the hands or feet |
Extreme pain | During physical activity |
Temperature sensitivity | Heat or cold intolerance |
Eye changes | Cornea verticillata — an abnormal eye pattern that does not affect vision and can only be seen during a slit-lamp eye exam |
Dizziness | Episodes of lightheadedness |
Flu-like symptoms | Fatigue, fever and body aches |
Digestive problems | Diarrhea, constipation and abdominal pain |
Ear problems | Hearing loss or ringing in the ears (tinnitus) |
Proteinuria | High levels of protein in urine |
Angiokeratomas | Raised, darker skin lesions on the chest, back and genital area |
Hypohidrosis / anhidrosis | Sweating less than normal, or not at all |
Edema | Swelling in the legs, ankles or feet |
What Causes Fabry Disease?
A genetic mutation of the galactosidase alpha (GLA) gene causes Fabry disease. The GLA gene produces the alpha-GAL enzyme that helps break down fatty substances called sphingolipids. People who inherit a defective GLA gene do not produce enough alpha-GAL enzyme [1]. As a result, fatty substances build up in their blood vessels.
Complications of Fabry Disease
Years of buildup of the fatty substance can damage blood vessels and lead to life-threatening issues.
Complication | What It Includes |
|---|---|
Heart problems | Arrhythmia, heart attacks, enlarged heart, heart failure |
Kidney failure | Loss of kidney function |
Nerve damage | Peripheral neuropathy |
Brain and circulation | Strokes, including transient ischemic attacks (TIAs, or ministrokes) |
How Is Fabry Disease Diagnosed?
Your healthcare provider may order tests to diagnose Fabry disease.
Diagnostic Test | What It Measures | Key Facts |
|---|---|---|
Enzyme assay | Alpha-GAL enzyme activity in the blood | Measurements of 1% or lower indicate disease; only reliable for men and not suited for women |
Genetic testing | GLA gene mutation via DNA sequencing | Used because some men with Fabry disease can have normal alpha-GAL enzyme activity |
Newborn screening | Tests for Fabry disease and other lysosomal storage disorders | Offered in some states |
How Is Fabry Disease Treated?
There is no cure for Fabry disease. Medications for pain and stomach problems can ease symptoms. Two Fabry disease treatments may slow down the buildup of fatty substances, with the goal of preventing heart problems, kidney disease and other life-threatening complications.
Treatment | How It Works | Key Details |
|---|---|---|
Enzyme replacement therapy (ERT) | Intravenous infusion every two weeks of a lab-made enzyme that does the work of the missing alpha-GAL enzyme | Currently available options are agalsidase beta (Fabrazyme) and pegunigalsidase alfa (Elfabrio); an antihistamine may be given before therapy to prevent allergic reactions; infusions take place at an infusion center or at home if tolerated well |
Oral chaperone therapy | Chaperones are small molecules that repair faulty alpha-GAL enzymes so they can break down the fatty substance again | Taken as a pill (migalastat, Galafold) every other day; does not work for everyone — eligibility depends on your specific GLA gene mutation |
Researchers are actively developing several new therapies using genetic engineering and stem cell technologies.
Outlook and Prognosis
Fabry disease is a progressive disease. Symptoms and the risk of serious complications worsen with age. People with Fabry disease have a higher risk of life-threatening problems that can shorten life expectancy.
On average, men with classic Fabry disease tend to live to their late 50s. Women with the disease often live into their 70s. You may add years to your life by getting appropriate care for heart and kidney disease and taking steps to reduce strokes.
Can Fabry Disease Be Prevented?
Fabry disease is inherited, so it cannot be prevented in the usual sense. If you carry the mutated gene that causes Fabry disease, talk to a genetic counselor. This specialist can explain the chances of passing the gene to your children and discuss options.
For instance, a process called preimplantation genetic diagnosis (PGD) identifies embryos that do not carry the mutated gene. Your healthcare provider implants healthy embryos during in vitro fertilization (IVF). PGD ensures your child will not have the disease.
Prevention Step | What It Involves |
|---|---|
Genetic counseling | Explains the chances of passing the gene to your children and discusses family-planning options |
Preimplantation genetic diagnosis (PGD) | Identifies embryos without the GLA mutation |
In vitro fertilization (IVF) with healthy embryos | Ensures the child will not have the disease |
When to Seek Care
If you experience burning, numbness or pain in your hands and feet — especially alongside digestive problems, unusual skin lesions or reduced sweating — or if Fabry disease runs in your family, ask your healthcare provider about testing. Early diagnosis makes treatment most effective.
Schedule an appointment with a healthcare provider or a genetic counselor if Fabry disease runs in your family or if you notice unexplained burning pain in your hands and feet. Specialists in metabolic and genetic medicine can arrange enzyme and genetic testing, and genetic counselors can discuss family-planning options.
Key Takeaways
Fabry disease is a rare, inherited lysosomal storage disorder in which a mutated GLA gene starves the body of the alpha-GAL enzyme it needs to break down fat-like sphingolipids. Those fats quietly accumulate in blood vessels and tissues for years, affecting the heart, kidneys, brain, nerves and skin — and raising the risk of heart attack, stroke and kidney failure. Classic Fabry disease affects about 1 in 40,000 men and begins in childhood, often with burning hands and feet; the late-onset form affects roughly 1 in 1,500 to 4,000 men and may first surface as kidney failure or heart disease in adulthood. There is no cure, but enzyme replacement therapy every two weeks and chaperone pills every other day can slow the fat buildup and prevent the most dangerous complications. If Fabry disease runs in your family, a genetic counselor can explain inheritance risks and options such as preimplantation genetic diagnosis with IVF — so the disease does not have to be passed to the next generation.
Take the Next Step
If unexplained burning, numbness or pain in your hands and feet is part of your life — especially alongside digestive symptoms, skin lesions or reduced sweating — ask your provider about Fabry disease testing. Early diagnosis is the key to protecting your heart, kidneys and quality of life.
Frequently Asked Questions
1. What is Fabry disease?
Fabry disease is a rare genetic lysosomal storage disorder in which the body does not produce enough of the alpha-galactosidase A (alpha-GAL) enzyme, which breaks down fat-like substances called sphingolipids. These fats collect in blood vessels and tissues, affecting the heart, kidneys, brain, central nervous system and skin, and raising the risk of heart attack, stroke and kidney failure.
2. What causes Fabry disease?
A genetic mutation of the GLA gene (galactosidase alpha) causes Fabry disease. The GLA gene produces the alpha-GAL enzyme that breaks down fatty substances (sphingolipids). People who inherit a defective GLA gene do not produce enough alpha-GAL enzyme, so fatty substances build up in their blood vessels.
3. Is Fabry disease hereditary?
Yes. People with Fabry disease inherit a mutated GLA gene on their X chromosome from a biological parent. Affected fathers pass the mutation to all daughters (sons are not at risk), while affected mothers have a 50% chance of passing it to each child.
4. How common is Fabry disease?
Approximately 1 in 40,000 men have classic Fabry disease. Late-onset (atypical) Fabry disease is more common, affecting about 1 in 1,500 to 4,000 men. Experts are not sure how many women are affected, as the condition frequently goes undiagnosed.
5. What are the symptoms of Fabry disease?
Symptoms include numbness, tingling, burning or pain in the hands and feet; extreme pain during physical activity; heat or cold intolerance; an abnormal eye pattern (cornea verticillata); dizziness; flu-like symptoms; gastrointestinal problems such as diarrhea, constipation and abdominal pain; hearing loss or tinnitus; protein in the urine; raised darker skin lesions (angiokeratomas); reduced or absent sweating; and swelling in the legs, ankles or feet.
6. Is Fabry disease more severe in men or women?
Men tend to have more severe Fabry disease symptoms than women. Some women have no symptoms or only mild symptoms that are easy to dismiss, which is why the condition frequently goes undiagnosed in women.
7. What are the complications of Fabry disease?
Years of fatty-substance buildup can damage blood vessels and lead to heart problems (arrhythmia, heart attacks, enlarged heart, heart failure), kidney failure, peripheral neuropathy (nerve damage), and strokes, including transient ischemic attacks (TIAs or ministrokes).
8. How is Fabry disease diagnosed?
An enzyme assay measures alpha-GAL enzyme activity in the blood — measurements of 1% or lower indicate disease, though this test is only reliable for men. Genetic testing (DNA sequencing) identifies the GLA gene mutation, and some states screen newborns for Fabry disease and other lysosomal storage disorders.
9. Is there a cure for Fabry disease?
No, there is no cure. However, two therapies may slow the buildup of fatty substances to prevent heart problems, kidney disease and other life-threatening complications: enzyme replacement therapy (an IV infusion every two weeks of agalsidase beta or pegunigalsidase alfa) and oral chaperone therapy (a migalastat pill taken every other day, if your specific GLA mutation is eligible).
10. What is the life expectancy with Fabry disease?
Fabry disease is progressive, and complications can shorten life expectancy. On average, men with classic Fabry disease tend to live to their late 50s, while women with the disease often live into their 70s. Appropriate heart and kidney care and stroke prevention may add years to life.
11. Can Fabry disease be prevented?
The disease itself is inherited and cannot be prevented, but a carrier can speak with a genetic counselor about options such as preimplantation genetic diagnosis (PGD), which identifies embryos without the GLA mutation so they can be implanted during IVF — ensuring the child will not have the disease.
References
Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry's disease with the pharmacologic chaperone migalastat. N Engl J Med. 2016;375(6):545-555. doi:10.1056/NEJMoa1510198. PMID: 27509102.
Medical Disclaimer
This article is for informational purposes only and does not constitute medical advice. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read here.
Comments