What is Fabry disease?

Fabry disease is a rare, inherited disorder caused by a deficiency of the enzyme alpha-galactosidase A. This deficiency leads to the accumulation of a substance called globotriaosylceramide (GL-3) in cells throughout the body, particularly in the kidneys, heart, and blood vessels. Symptoms of Fabry disease can include pain in the hands and feet, skin rashes, and kidney problems. In severe cases, the disease can lead to kidney failure, heart attack, or stroke. There is no cure for Fabry’s disease, but enzyme replacement therapy can help manage symptoms and slow the progression of the disease. Genetic counseling is recommended for individuals with a family history of Fabry disease.

A urologist is a medical doctor who specializes in the treatment of conditions that affect the urinary tract in both women and men.

What are the types of Fabry disease?

There are two types of Fabry disease:

 classic and later-onset.

• Classic Fabry disease is the more severe form of the disorder, and symptoms usually appear in childhood or adolescence. Symptoms can include severe burning and tingling pain in the hands and feet, skin rashes, and kidney problems. Over time, classic Fabry disease can lead to kidney failure, heart attack, or stroke.
• Later-onset Fabry disease is a milder form of the disorder, and symptoms may not appear until adulthood. Symptoms can include milder pain in the hands and feet, skin rashes, and kidney problems. Later-onset Fabry disease may not cause as much organ damage as classic Fabry disease, and some individuals may not develop serious complications.

It is worth noting that these are general distinctions and the symptoms and progression of the disease can vary widely among affected individuals.

What causes Fabry’s disease?

Fabry disease is caused by a deficiency of the enzyme alpha-galactosidase A (α-Gal A). This enzyme is responsible for breaking down a substance called globotriaosylceramide (GL-3), which is found in cells throughout the body. When α-Gal A is deficient, GL-3 accumulates in cells, particularly in the kidneys, heart, and blood vessels. This accumulation of GL-3 leads to the characteristic symptoms of Fabry disease.

The disease is inherited in an X-linked recessive manner, which means that it is caused by a mutation in the GLA gene located on the X chromosome. As the mutation is located on the X chromosome, men are more frequently affected than women.

Women who carry a copy of the GLA gene mutation on one of their X chromosomes are called carriers. They may have mild symptoms or may not have symptoms at all. However, they can pass the disease on to their children.

Who might get Fabry disease?

Fabry disease is a rare genetic disorder, affecting about 1 in 40,000-117,000 people worldwide. It is caused by mutations in the GLA gene, which is located on the X chromosome. As a result, it is inherited in an X-linked recessive manner. This means that the disorder primarily affects males, who have only one X chromosome, while females who have two X chromosomes are usually carriers of the disease.

Fabry disease can occur in all ethnic groups and it is not limited to any specific geographic region. It is estimated that around 1 in every 2,500 males has Fabry disease. However, because the disease can have a wide range of symptoms and can be mild or severe, many people may not be diagnosed.

It’s important to note that people who have a family history of Fabry disease or who have symptoms that may be consistent with the disease should talk to a doctor or genetic counselor about getting tested for the disorder.

What are the symptoms of Fabry’s disease?

The symptoms of Fabry disease can vary widely among affected individuals and can range from mild to severe.

Common symptoms include:

• Pain in the hands and feet: This can be a burning or tingling sensation, which is often described as “pins and needles” or “like being burned with hot wax.” In severe cases, the pain can be debilitating and can interfere with daily activities.
• Skin rashes: Some people with Fabry disease develop small, red, raised spots on the skin, called angiokeratomas, which are caused by the accumulation of GL-3 in blood vessels. These rashes typically appear on the trunk, lower back, and upper thighs.
• Gastrointestinal symptoms: Some people may have episodes of diarrhea, constipation, abdominal pain, or nausea.
• Cardiac and cerebrovascular symptoms: Fabry disease can cause damage to the heart and blood vessels, which can lead to heart attack, stroke, or high blood pressure.
• Kidney problems: Over time, the accumulation of GL-3 in the kidneys can lead to chronic kidney disease, which may progress to kidney failure.
• Hearing loss, ringing in the ears (Tinnitus), and vision problems: Some people may experience hearing loss, ringing in the ears, or vision problems.

It’s important to note that symptoms of Fabry disease can be mistaken for other conditions, and many people may not be diagnosed until they are adults.

How is Fabry’s disease diagnosed?

Fabry disease is diagnosed through a combination of genetic testing and clinical evaluation.

The following tests may be used to diagnose Fabry disease:

• Genetic testing: This test looks for mutations in the GLA gene, which is responsible for producing the alpha-galactosidase A enzyme. Genetic testing can confirm a diagnosis of Fabry disease and can also help identify carriers of the disease.
• Enzyme testing: This test measures the level of alpha-galactosidase A enzyme in the blood. A deficiency of this enzyme is the key characteristic of Fabry disease.
• Biopsy: A small sample of skin or kidney tissue may be taken and examined under a microscope to look for signs of GL-3 accumulation.
• Cardiac and cerebrovascular imaging: This test can be used to evaluate the health of the heart and blood vessels. It can detect any damage caused by GL-3 accumulation and can also help to monitor the progression of the disease.
• Kidney function tests: These tests can be used to evaluate the health of the kidneys and to detect any damage caused by GL-3 accumulation.

It’s important to note that Fabry’s disease can be mistaken for other conditions, so a careful and comprehensive evaluation is needed for accurate diagnosis.

How is Fabry’s disease managed or treated?

There is currently no cure for Fabry’s disease, but treatment can help to manage symptoms and slow the progression of the disease. The treatment options include:

• Enzyme replacement therapy (ERT): This treatment replaces the missing alpha-galactosidase A enzyme, which helps to break down GL-3 and reduce its accumulation in cells. This treatment can help to reduce pain, slow the progression of kidney disease, and reduce the risk of heart attack and stroke.
• Chaperone therapy: This treatment helps to stabilize and increase the activity of the remaining alpha-galactosidase A enzyme that is produced by the body, this is a less common treatment used in patients with specific mutations.
• Pain management: Pain can be treated with over-the-counter pain relievers or with prescription medications. Some people may also benefit from physical therapy or occupational therapy to help manage pain and improve function.
• Kidney disease management: If kidney disease is present, treatment may include medications to control blood pressure and reduce the risk of kidney failure. In advanced stages of kidney disease, dialysis or transplantation may be necessary.
• Cardiac and cerebrovascular management: If heart or blood vessel problems are present, treatment may include medications to control blood pressure, lower cholesterol levels, and prevent blood clots.
• Supportive care: Genetic counseling, regular monitoring by a specialist in Fabry disease, and support from a disease-specific patient organization can also be beneficial for people with Fabry disease.

It’s important to note that the treatment plan for Fabry’s disease is tailored to the individual and may change over time as the disease progresses. Regular monitoring by a specialist in Fabry disease is important to ensure that treatment is effective and to detect any complications early.

Conclusion

In conclusion, Fabry disease is a rare, inherited disorder caused by a deficiency of the enzyme alpha-galactosidase A. This deficiency leads to the accumulation of a substance called globotriaosylceramide (GL-3) in cells throughout the body, particularly in the kidneys, heart, and blood vessels. Symptoms of Fabry disease can include pain in the hands and feet, skin rashes, and kidney problems. In severe cases, the disease can lead to kidney failure, heart attack, or stroke. There is no cure for Fabry’s disease, but enzyme replacement therapy and chaperone therapy can help manage symptoms and slow the progression of the disease. Genetic counseling is recommended for individuals with a family history of Fabry disease. Regular monitoring by a specialist in Fabry disease is important to ensure that treatment is effective and to detect any complications early.