Fabry disease, from early signs to critical symptoms

Fabry is a rare genetic disease caused by a variant, or mutation, in the GLA gene. The gene provides the plan for an enzyme called alpha galactosidase (alpha-Gal A). In Fabry disease, variants can cause the alpha-Gal A enzyme to be either absent or deficient. It usually would travel into the lysosome , the recycling center of the cell, to break down fatty substances, or substrates. But in Fabry, with the alpha-Gal A enzyme being absent or deficient, the important job is left undone. Without this enzyme present to break down the substrates, the fatty substances build up instead. The substance buildup can cause damage to cells and lead to symptoms of the disease.

Fabry symptoms in men and women

Both men and women with Fabry disease can experience symptoms. It used to be thought that when women have variants that can cause Fabry disease, they do not experience symptoms. We now know that most women who have variants in the GLA gene do experience the effects of Fabry, often as severely as men with Fabry disease.

There can be differences in the ways females with Fabry and males with Fabry inherit the disease. This difference has to do with genetics. Variants that cause Fabry are located on the X chromosome, and because men have only one X chromosome, Fabry disease can present in each cell. Women have two X chromosomes, with one of the two chromosomes activated in each cell. Women with Fabry may experience all or just some of the effects of Fabry to different extents, or they might never feel any of them. But if you are a woman who is experiencing symptoms of Fabry, you are in the majority. Nearly 70% of women diagnosed with Fabry report having signs and symptoms of the disease.

Different types of Fabry

Fabry symptoms can vary from person to person, and the disease can affect different areas of the body. Fabry presents along a spectrum, with symptoms ranging in severity from mild to severe. The timing for when symptoms start can also vary greatly from person to person. A Fabry diagnosis can take time because Fabry disease symptoms can be similar to other disease symptoms. While a Fabry disease diagnosis can be confirmed in some people with a blood test, you may be able to work with a healthcare provider to determine the kind of Fabry you have using a genetic test. For example, a Fabry diagnosis can only be confirmed in women through a genetic test.

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  Classic Fabry in males: This type of Fabry can cause many severe symptoms beginning in early childhood and can lead to serious organ damage.
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  Classic Fabry in females: Symptoms can present during childhood or later in life and range in severity from mild to severe.
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  Late-onset Fabry: People with this type (both male and female) have some alpha-Gal A enzyme activity and may not experience symptoms until they are adults.
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  Late-onset cardiac/renal: Certain variants may lead to late-onset Fabry affecting primarily the heart (cardiac) or the kidneys (renal).
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  Uncertain significance: Variants of uncertain significance either lack enough evidence or have conflicting evidence of their ability to cause Fabry disease. A person with a variant of uncertain significance may or may not experience Fabry disease symptoms.

An invisible illness

Because some Fabry symptoms are invisible from the outside, it can be difficult to talk about your symptoms with others, especially in the workplace and even to your loved ones. Know that other people living with Fabry have been where you are. While your disease may be invisible, you aren’t alone.

Serious consequences

Life-threatening Fabry consequences may arise because Fabry disease can affect vital organs that maintain proper bodily function. Below you’ll see what to look out for.

Kidneys

(renal manifestations of Fabry disease)

• Decreased kidney function
• Kidney failure
• Need for kidney transplantation

Heart

(cardiac manifestations of Fabry disease)

• Irregular heartbeat (fast or slow)
• Heart disease
• Heart attack or heart failure
• Enlarged heart

Brain

(cerebral manifestations of Fabry disease)

• Transient ischemic attack (TIA)
• Stroke

Early signs and symptoms

Common early symptoms of Fabry disease that people may report can include pain in the hands and feet, the inability to sweat or lack of sweating, and gastrointestinal symptoms including nausea and abdominal distress. Other early signs of Fabry disease that may lead to a Fabry diagnosis are a whorled pattern in the corneas of the eyes and Fabry cataracts. This whorled pattern can sometimes be detected during an eye exam.

Common symptoms

Pain is the most common Fabry symptom that people diagnosed with Fabry report. Pain has been described by people with the symptom as a “burning,” “stabbing,” and/​or “tingling.” 66% of people with Fabry experience pain caused by something else—in other words, pain that is triggered by physical activity or changes in temperature. Episodes of pain can be short or go on for days, often called a “pain crisis.”

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  Nervous system

  Fabry can affect the nervous system, causing nerve pain; an intolerance to heat, cold, or exercise; and vertigo or feeling dizzy.

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  Psychological

  Fabry disease can cause psychological symptoms. People may have feelings of guilt, worry, depression, isolation, and/or fear.

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  Skin

  Fabry disease can affect the skin, with some people with Fabry sweating less than normal or not at all. This effect can lead to problems with tolerating heat and exercise. Another symptom is skin lesions or small, dark, red spots. These skin lesions, called angiokeratomas, could appear between the belly button and upper thighs.

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  Lungs

  The lungs of people with Fabry can be affected, with some people experiencing wheezing, difficulty breathing, shortness of breath, bronchitis, or chronic cough.

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  Hearing

  People with Fabry can also have hearing loss or hear a ringing in the ears (tinnitus).

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  Other additional symptoms

  Fatigue, or a deep feeling of tiredness, can occur.

Fabry is a progressive disease

When a disease is progressive, it means that it can change over time. Fabry symptoms can get worse and severe symptoms can arise. The disease can change slowly or quickly, causing damage at different rates. Whether you feel its effects or not, it may be getting worse and symptoms may change from what they are today. Damage may occur in one or more vital organs such as the kidneys, heart, and brain, as detailed above.

Waiting on your management might not be an option for you, so make sure you know what it means to be proactive on progression.