What is Fabry Disease?
Fabry disease is a condition that impacts multiple systems in the body. This illness, which is linked to the X-chromosome, comes from a decrease in the activity of a specific enzyme called alpha-galactosidase A. This leads to a build-up of certain types of fats, called neutral glycosphingolipids and globotriaosylceramide GL-3, in the body’s cells. A common skin condition seen in people with Fabry disease is called Angiokeratoma corporis diffusum, which is often linked to kidney problems, particularly protein in urine.
If a young adult experiences a sudden brain event, like a stroke, alongside a heart attack and kidney dysfunction, doctors may suspect Fabry disease. This condition can cause abnormalities almost anywhere in the body, with a higher likelihood of affecting the skin, eyes, kidneys, heart, brain, and peripheral nervous system, which connects the brain and spinal cord to the rest of the body.
What Causes Fabry Disease?
Fabry disease is caused by a large number of changes, or mutations, in a gene called alpha-Gal A. This gene is found on the X chromosome. This disease leads to low levels of the alpha-Gal A, which is important in preventing the buildup of a certain kind of fat, mostly cerebroside trihexosides, in parts of your body’s cells known as the lysosomes.
As this fat accumulates, it can cause the cells that line your blood vessels to swell and multiply. This can lead to kidney failure between the ages of 30 and 40, heart disease, strokes, and can shorten your lifespan.
The regular form of Fabry disease, called the ‘classic Fabry phenotype’, is associated with these genetic mutations and can affect many different body systems. However, for milder forms of the disease, which are usually caused by ‘missense’ genetic mutations, the problems are usually restricted to the heart. Note, a missense mutation is a type of mutation where one genetic code letter is replaced by another, which results in a different amino acid being incorporated into a protein. This can affect the structure and function of the protein, potentially causing disease.
Risk Factors and Frequency for Fabry Disease
Fabry disease is a condition seen in all racial and ethnic groups. However, it’s more commonly found in white men. The prevalence varies greatly, with estimates ranging from 1 in 17,000 to 1 in 117,000. The classic form of Fabry disease occurs in about 1 in 22,000 to 1 in 40,000 males. Atypical or less common forms of the disease are found in approximately 1 in 1,000 to 1 in 3,000 males and 1 in 6,000 to 1 in 40,000 females. Despite these numbers, Fabry disease is often under-diagnosed.
- Fabry disease is most commonly seen in white males.
- The estimated prevalence ranges between 1 in 17,000 and 1 in 117,000.
- Classic Fabry disease occurs in about 1 in 22,000 to 1 in 40,000 males.
- Atypical forms are found in 1 in 1,000 to 1 in 3,000 males and 1 in 6,000 to 1 in 40,000 females.
- The disease is usually under-diagnosed.
Signs and Symptoms of Fabry Disease
The patient’s history can reveal high blood pressure linked to kidney problems. A comprehensive medical history is essential, with a focus on symptoms like not being able to tolerate heat well and significantly less sweating and tear production. Other factors to consider include severe heart conditions and stroke incidents. Another important aspect is the family history due to the disease’s tendency to pass on through an X-linked pattern. The disease often appears among male patients during their childhood or early teenage years and it could affect any organ system in the body.
It commonly brings symptoms such as :
- Painful sensitivity or numbness in the extremities (acroparesthesias)
- Reduced sweat production (hypohidrosis)
- Stomach pains and diarrhea
Skin problems may include small, rash-like spots around the belly button. Eye complications may involve conditions like lenticular opacities and corneal dystrophy.
How the disease progresses can vary, but it usually shows as excessive urination, excessive thirst, and protein in urine leading to final-stage kidney disease. Other possible manifestations include defects in the heart’s electric signaling system and valves, stroke, and other neurological problems happening from the third to the fourth decade of life. Some patients may have enlarged lymph nodes and struggle with temperature changes and intense physical activity.
Testing for Fabry Disease
If you’re experiencing the symptoms we previously discussed, plus having both personal and family history aligning with it, there’s a chance you might have Fabry disease. This is why your doctor might be deeply suspicious of this condition. To get a clearer picture, a set of tests will likely be ordered.
These tests involve a basic metabolic profile that includes checking the substance levels in your body (like electrolytes) and evaluating how well your kidneys are functioning. You may also have a urine sample taken to search for certain types of fat that could indicate damage to the kidney. An ECG, which is essentially an advanced heartbeat monitor, might be used alongside an echocardiogram — a type of ultrasound for your heart — to check for any abnormalities in your heart’s structure or rhythm.
Further tests might include a chest x-ray or different types of scans (such as CT, CTA, MRI, MRA, and MR spectroscopy) to check for any neurological abnormalities (changes to your nervous system, which includes your brain and nerves).
An essential decisive test for Fabry disease involves measuring the activity of an enzyme (a protein that helps involved in body processes) called alpha-Gal A in your white blood cells or plasma (the liquid part of your blood). If this enzyme is less active than usual, it’s a clear sign of Fabry disease.
If enzyme activity analysis or genetic testing isn’t available in your scenario, a sample of your skin or kidney may be taken for testing. These samples will be examined under a microscope looking for abnormal deposits of a certain type of fat (glycolipids). Such deposits are a distinctive sign of Fabry disease. Detailed checking with an electron microscope (a very powerful microscope) may show special types of inclusions (trapped particles) called myeloid or zebra bodies, which also suggest Fabry disease.
Treatment Options for Fabry Disease
Fabry disease is a condition that cannot be fully cured, but it can be managed with proper treatment. One of the main ways to treat Fabry disease is by replacing a missing enzyme called alpha-galactosidase A. Doctors typically suggest this treatment as soon as Fabry disease is diagnosed, even if the patient doesn’t have any visible symptoms yet, particularly for men affected by the disease and patients receiving kidney replacement therapy.
For affected males with lowered levels of this enzyme and female carriers of the disease, they should consider enzyme replacement only if they start showing symptoms related to the kidneys, heart, or brain. When someone with Fabry disease is on long-term dialysis, they too should receive enzyme replacement therapy to manage their condition. High blood pressure, often present in Fabry disease patients, should be controlled with medication like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
The enzymes (either alpha or beta kind) are typically given via infusion every two weeks. This involves directly putting the enzymes into the bloodstream through a drip. It’s important to take precautions to avoid any reactions related to these infusions. Doctors may suggest a slow infusion over a couple of hours and may give medications to control any side effects.
For people with Fabry disease who eventually require a kidney transplant, it’s reassuring to know that they can safely receive a new kidney. After the transplant, it is recommended to continue enzyme replacement therapy to manage their condition.
What else can Fabry Disease be?
- Stroke
- Cavernous sinus syndromes
- Lacunar syndromes
- Multiple sclerosis
What to expect with Fabry Disease
When a person has their first stroke, there’s a likelihood they could experience more strokes in the future. This is quite common.
Also, in the context of genetic conditions, females who have a variant copy of a particular gene (heterozygous females) usually experience less severe symptoms compared to males.
Possible Complications When Diagnosed with Fabry Disease
- Angiokeratomas: A medical term referring to small, dark spots on the skin
- Cardiomegaly: An enlarged heart
- Arrhythmias: Irregular heart rhythms, which may be noticed as fluttering heartbeats, a racing heartbeat or a slow heart rate
- Acroparesthesia: Sensations like tingling, numbness or burning, usually in extremities like hands and feet
- Hearing loss: Reduced ability to hear sounds
- Vertigo: A sense of spinning or feeling unsteady
- Altered sweating: Changes in how much you sweat, which can be an increase or decrease
- Corneal verticillata: A condition causing spiral patterns on the cornea (the clear layer in front of the iris and pupil)
