Fabry Disease Awareness Month

What is Fabry Disease?

Fabry disease is a rare genetic condition in which a person doesn’t produce enough healthy versions of an enzyme called alpha-galactosidase A (alpha-GAL). This enzyme breaks down sphingolipids, a fat-like substance. Without functioning alpha-GAL enzymes, harmful levels of sphingolipids build up in blood vessels and tissues. In addition, Fabry disease affects the heart, kidneys, brain, central nervous system and skin. Fabry disease is a type of lysosomal storage disorder.

Lastly, other names for the condition are 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. Types include:

• Classic type: Symptoms of classic Fabry disease appear during childhood or the teenage years. One common disease symptom, a painful burning sensation in the hands and feet, may be noticeable as early as age 2. In addition, symptoms get progressively worse over time.
• Late-onset/atypical type: People with late-onset Fabry disease don’t have symptoms until they’re in their 30s or older. The first indication of a problem, for example, may be kidney failure or heart disease.

How Common is Fabry Disease?

Approximately 1 out of every 40,000 men and people assigned male at birth (AMAB) has classic Fabry disease. However, late-onset or atypical Fabry disease is more common. It affects about 1 in every 1,500 to 4,000 men and people AMAB.

Experts aren’t sure how many women and people assigned female at birth (AFAB) have Fabry disease. Some women and people AFAB don’t have symptoms or have mild, easy-to-dismiss symptoms, so the condition frequently goes undiagnosed.

Who Might get Fabry Disease?

People with Fabry disease inherit a mutated gene on their X chromosome from a biological parent. Men and people AMAB inherit one X chromosome from their female parent. Women and people AFAB 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. For example,

• Male parents with Fabry disease pass their X chromosome with the faulty gene to all of their daughters. All these daughters will have the gene mutation that causes Fabry disease. Sons aren’t at risk because males get the Y chromosome from their male parent (not the X chromosome).
• Female parents with Fabry disease have a 50% chance of passing their affected X chromosome to their daughters or sons. Some family members can have the gene mutation while others don’t.

What are the 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 and people AMAB tend to have more severe Fabry disease symptoms than women and people AFAB. Fabry disease symptoms include:

• Numbness, tingling, burning or pain in the hands or feet.
• Extreme pain during physical activity.
• Heat or cold intolerance.
• Abnormal pattern of the eye (cornea verticillata), which doesn’t affect vision and can only be seen during an eye exam with a slit lamp.
• Dizziness.
• Flu-like symptoms, including fatigue, fever and body aches.
• Gastrointestinal problems, such as diarrhea, constipation and abdominal pain.
• Hearing loss or ringing in ears (tinnitus).
• High levels of protein in urine (proteinuria).
• Raised darker skin lesions (angiokeratoma) on the chest, back and genital area.
• Sweating less (hypohidrosis) or not at all (anhidrosis).
• Swelling (edema) in the legs, ankles or feet.

Causes

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 (sphingolipids). People who inherit a defective GLA gene don’t produce enough alpha-GAL enzyme. As a result, fatty substances build up in their blood vessels.

Complications

Years of buildup of the fatty substance can damage blood vessels and lead to life-threatening issues, including:

• Heart problems, including arrhythmia, heart attacks, enlarged heart and heart failure.
• Kidney failure.
• Nerve damage (peripheral neuropathy).
• Strokes, including transient ischemic attacks (TIA or ministrokes).