Fabry Disease
Fabry disease is a rare inherited condition where the body does not make enough of an enzyme called alpha-galactosidase A.
Overview
Fabry disease is a rare inherited condition where the body does not make enough of an enzyme called alpha-galactosidase A. This enzyme normally breaks down a fatty substance in the body. Without enough of it, fatty material accumulates in cells throughout the body. Over time, this build-up can damage important organs such as the kidneys, heart, brain, skin, and nerves. Fabry disease is a type of lysosomal storage disorder.
Causes and Genetics
Fabry disease is caused by changes (mutations) in the GLA gene. The GLA gene provides instructions for making the enzyme alpha-galactosidase A. When the enzyme does not work properly, a fatty substance called globotriaosylceramide (Gb3) accumulates within the body. Fabry disease is inherited in an X-linked pattern meaning that males are often more severely affected, however females may have mild, moderate, or severe symptoms.
Symptoms and Features
Characteristic Symptoms and Features
- Burning or tingling pain in the hands and feet (acroparesthesia), often triggered by heat or exercise
- Small dark red or purple skin spots (angiokeratomas), usually around the lower trunk
- Reduced ability to sweat (hypohidrosis)
- Characteristic eye findings (corneal verticillata), usually only detected during an eye examination
Other Associated Symptoms and Features
- Abdominal pain, diarrhea, constipation
- Hearing loss or ringing in the ears (tinnitus)
- Dizziness and headaches
- Protein in the urine
- Progressive kidney disease
- Enlarged heart or abnormal heart rhythm
- Increased risk of stroke
Symptoms can begin in childhood but may worsen over time.
Treatment
Supportive treatments are essential to look after a person's organs and health and wellbeing. These include pain management medication, blood pressure lowering treatments, regular tests to monitor kidney function and heart health. In some people who develop specific organ complications, specialist treatments to support those organs are needed (for example dialysis or a kidney transplant in someone who develops severe kidney failure). Patients are usually managed through specialist metabolic centres.
Research and Future Directions
There is active research assessing newer ways to look after people with Fabry Disease. These include gene therapies (trying to insert a normal copy of the GLA gene to get a person's body to produce their own working enzyme), newer enzyme replacement treatments, treatments aimed at reducing the amount of the fatty substances that accumulates and also newer blood tests to both track the disease better and potentially allow more personalised treatments for people with Fabry Disease. Importantly, there is also ongoing research into quality-of-life features, for example how best to manage pain and help people manage their day-to-day lives when living with the condition.