Fabry disease

Fabry disease can be associated with a wide range of severity and it is commonly divided into two types, "classic" and "non-classic or late onset." Both men and women can have classic and non-classic Fabry disease. Because of the way Fabry disease is passed through families, symptoms often vary more in women than in men. The type of Fabry disease often depends on the age symptoms start, the organs affected by the disease, how fast the disease progresses, and how severe symptoms become.

Classic Fabry disease symptoms in males and females typically start in the first 2-10 years of life with the onset of burning pain in the hands and feet, heat intolerance and gastrointestinal issues, such as diarrhea, pain and constipation. Without treatment the classic form of the disease progresses into the kidneys, heart, and causes other health problems to occur between the ages of 20 to 45.

In non-classic Fabry disease, symptoms may start after childhood and may more severely affect one organ like the heart or kidneys. It is important to note that in non-classic Fabry disease, heart disease and other symptoms still occur earlier than average in men than women, so it is important to monitor the heart, kidneys, and brain from the time of diagnosis with Fabry disease. In both classic and non-classic Fabry disease, symptoms always worsen over time.

Rarely, Classic Fabry disease will be referred to as "Type I" and Non-Classic Fabry disease will be referred to as 'Type II" but that is not the preferred terminology.

To learn more about classic and non-classic Fabry disease, please talk to your doctor or speak with a Fabry center team member. Find a Fabry center near you at the National Fabry Disease online resource.

Fabry disease is a progressive genetic condition that causes health problems like extreme tiredness (fatigue), little to no sweating (hypohidrosis), whorls in the cornea of the eyes (cornea verticillata), reddish-purplish skin rashes (angiokeratomas), burning pain in the hands and feet (neuropathic pain), problems in the heat and cold, frequent diarrhea and constipation, protein in the urine, and slow heartbeat (bradycardia). Without treatment, Fabry-related health problems will worsen leading to heart disease, kidney disease, and increased risk for strokes. Fabry disease occurs when a person's body does not make enough of an enzyme called alpha-galactosidase A (alpha-Gal) due to changes or mutations in the GLA gene. When alpha-gal is not working, substances called glycolipids [globotriaosylceramide (GL-3 or GB3) and lyso-globotriaosylceramide (Lyso-GL3 or LysoGB3)] build up in the body's lysosomes (the "recycling centers" of the cell). This storage leads to narrowed blood vessels, inflammation, and health problems all over the body, particularly in the skin, kidneys, heart, brain, intestines and nerves.

Fabry disease can be associated with a wide range of symptoms but is commonly divided into two types, "classic" and "non-classic" or "later onset." Both men and women can have classic and non-classic Fabry disease. Because of the way Fabry disease is passed through families, symptoms often vary more in women than in men. The type of Fabry disease often depends on the age symptoms start, the organs affected by the disease, how fast the disease progresses, and how severe symptoms become. Classic Fabry disease symptoms in males and females typically start in the first 2-10 years of life with the onset of burning pain in the hands and feet, decreased sweating, problems in the heat, a reddish-purplish rash, and gastrointestinal issues such as diarrhea, bloating, pain, and constipation. Without treatment, the classic form of the disease progresses into kidney disease, heart disease, and increased stroke risk between the ages of 20 to 45. In non-classic Fabry disease, symptoms may start somewhat later in life and may more severely affect one organ like the heart or kidney. In non-classic Fabry disease, heart disease and other symptoms still occur earlier than average in men than women, so it is important to monitor the heart, kidneys, and brain from the time of diagnosis with Fabry disease. In both classic and non-classic Fabry disease, symptoms always worsen over time.

Currently, there is no cure for Fabry disease; however, there are two Food & Drug Administration (FDA) approved medications in the United States that can help stabilize or prevent the progression of the more serious health problems if started early in the disease's course. Fabrazyme®, or agalsidase beta, is an enzyme replacement therapy (ERT) usually given every two weeks by IV to break down the stored glycolipids in the body. Fabrazyme® is a treatment that can be given to individuals with any mutation or change in the GLA gene. Migalastat or Galafold® is a pill taken every other day that is designed to help an individual with Fabry disease's own enzyme work more effectively (chaperone therapy). Galafold® only works for specific mutations in the GLA gene that are considered "amenable". Individuals with Fabry disease can talk to their doctors to learn if they may be able to take Galafold and check to see if their GLA change is considered amenable at the GLA mutation search website.

Outside of the United States, a second enzyme replacement therapy (ERT) medication for Fabry disease is available called Replagal® (agalsidase alfa). Replagal® is a treatment that can be given to individuals with any mutation or change in the GLA gene.

There are symptom specific treatments available to help relieve some of the other health problems of Fabry disease and there are also support networks to help individuals cope with the day-to-day struggles of living with Fabry disease such as the Fabry Support and Information Group (FSIG) and the National Fabry Disease Foundation (NFDF).

There is an excellent summary about Fabry disease written for doctors at Fabry Disease- GeneReviews.

Fabry disease can also be referred to as:

• Alpha-Galactosidase A deficiency
• Anderson-Fabry disease
• Angiokeratoma corporis diffusum
• Angiokeratoma diffuse
• Ceramide trihexosidase deficiency
• Fabry's disease
• GLA deficiency
• Hereditary dystopic lipidosis
• Fabry
• Late onset Fabry disease
• Later onset Fabry disease
• Classic Fabry disease
• Non-classic Fabry disease

Fabry disease (FD) is found in individuals of all different backgrounds, races, and ethnicities. Fabry disease occurs in a range of 1 in 1,250-117,000 live births worldwide.

Around 5,000 people in the U.S. have been diagnosed with Fabry disease. That number is a mixture of men and women living with Fabry disease, as well as a combination of people with classic and non-classic Fabry disease. However, doctors fully believe that many people living with Fabry disease have not been diagnosed due to the nonspecific health problems associated with the condition (e.g. severe tiredness, burning pain in the hands and feet). Newborn screening has increased the number of people diagnosed with Fabry disease, but it has also made things a little more complicated. Some newborns and their family members have new changes or variants of unknown significance in the GLA gene and it is unclear if these changes contribute to the health issues associated with Fabry disease.

Fabry disease (FD) is found in individuals of all different backgrounds and ethnicities around the world; however, there are a few places where it is seen more frequently. For example, there is an increased number of people in Nova Scotia, Canada with classic Fabry disease and in Taiwan with nonclassic Fabry disease.

The usual abbreviations for Fabry disease are FD or AFD.