Fabry disease is a rare, inherited condition that affects how the body breaks down certain fats. It occurs when the enzyme alpha-galactosidase A, which is responsible for removing a specific fatty substance called globotriaosylceramide (Gb3), is missing or doesn’t work properly. As a result, Gb3 builds up in many parts of the body, including the heart, kidneys, skin, and nervous system. Over time, this buildup causes inflammation and damage to these organs, leading to serious complications. 

Fabry disease is caused by changes, or mutations, in a gene called GLA, located on the X chromosome. This gene provides instructions for making the enzyme alpha-galactosidase A. When this enzyme doesn’t work correctly, certain fatty substances cannot be broken down and start to build up inside the body’s cells. Over time, that buildup interferes with how organs and tissues function, especially the heart, kidneys, and nervous system. 

Because Fabry disease is passed down through the X chromosome, it affects males and females differently. Males, who have only one X chromosome, usually show more severe symptoms, while females may have mild to severe signs depending on which X chromosome is active in their cells. This explains why some women experience symptoms similar to men, while others have only mild or delayed signs. 

There are two main forms of Fabry disease, which differ in when they appear and how they affect the body: 

• Classic Fabry disease: This type typically begins in childhood or the teenage years. It often causes pain, skin changes, and symptoms involving many organs, including the heart and kidneys. 

• Later-onset (non-classic) Fabry disease: This form appears later in life, usually in adulthood, and most often affects the heart or kidneys. People with this type may not experience the early pain or skin signs seen in the classic form. 

Understanding the genetic cause of Fabry disease is important because it helps guide testing and treatment for both the patient and family members who may also be at risk. 

The gradual buildup of Gb3 leads to a variety of symptoms that can affect nearly every system in the body: 

• Nerves: Burning pain or tingling in the hands and feet (especially during heat or exercise). 

• Skin: Clusters of small, dark red spots (angiokeratomas) often appear around the lower abdomen or groin. 

• Sweating: Reduced ability to sweat or complete absence of sweating. 

• Eyes: Whirl-like patterns on the cornea that usually do not affect vision. 

• Digestive system: Episodes of stomach pain, nausea, or diarrhea. 

As Fabry disease progresses, it can damage the kidneys, heart, and brain: 

• Kidneys: Protein in the urine, high blood pressure, and eventually kidney failure. 

• Heart: Thickened heart walls, irregular rhythms, and heart failure. 

• Brain: Increased risk of stroke, dizziness, or hearing problems. 

Because Fabry disease can mimic other conditions, diagnosis often takes years. Doctors typically confirm it using: 

• Blood enzyme test: Measures alpha-galactosidase A activity (low or absent in affected males). 

• Genetic testing: Identifies mutations in the GLA gene and is essential for diagnosing women. 

• Additional evaluations: Urine tests for protein, heart imaging, kidney function tests, and brain scans to assess organ involvement. 

Although Fabry disease has no cure, several treatments can significantly slow disease progression and improve quality of life: 

• Enzyme replacement therapy (ERT): Regular intravenous infusions (agalsidase alfa or beta) replace the missing enzyme and reduce Gb3 buildup. 

• Chaperone therapy: An oral medication called migalastat can help stabilize the defective enzyme in certain patients with specific mutations. 

• Supportive care: 
  • Pain management with nerve pain medications like gabapentin or duloxetine. 
  • ACE inhibitors or ARBs to protect kidney function. 
  • Heart medications or pacemakers for rhythm problems. 
  • Lifestyle steps such as staying hydrated, avoiding overheating, and eating a balanced diet. 

Without treatment, Fabry disease can lead to kidney failure, heart problems, and strokes at a relatively young age. Early diagnosis and treatment can prevent or delay many of these complications. People who begin enzyme replacement or chaperone therapy early often experience fewer pain episodes, slower organ damage, and a longer life expectancy. 

Living with Fabry disease can be challenging, but with proper care, many people lead fulfilling lives. Regular follow-up with specialists—including a cardiologist, nephrologist, neurologist, and genetic counselor—is essential. Family testing is also important since Fabry disease is inherited. 

Emotional support and patient advocacy groups can provide valuable help for managing the condition’s daily challenges and for connecting with others facing similar experiences. 

Fabry disease is serious but increasingly treatable. Advances in enzyme and gene therapies are improving long-term outcomes and giving patients new hope. Early detection remains key—the sooner Fabry disease is identified and treatment begins, the better the chances of preserving heart, kidney, and brain function for years to come. 

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3. Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease. J Med Genet. 2017;54(4):288–296. 

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