Fabry Disease

What Is Fabry disease?

Fabry disease is an X-linked recessive disorder due to the deficiency of the lysosomal enzyme alpha-galactosidase A, which helps in the metabolism of lipids. The enzyme alpha-galactosidase A is produced by the gene “galactosidose, alpha” or GLA. Once this gene mutates, then production of the enzyme alpha-galactosidose A would be deficient, if not absent. As an X-linked recessive disorder, this means that male offspring have 50 percent chance of having the disease while female offspring have 50 percent chance to be carriers.

Fabry Disease Symptoms

The common symptoms of Fabry disease, which usually begins in childhood or early adulthood, are the following:

• Acroparesthesia—pain and burning sensations in the hands and feet which is exacerbated by physical work, stress, and weather changes
• Angiokeratomas—dark red skin rash which often develop from the umbilicus to the knees
• Renal failure
• Cardiovascular complications—due to the insufficient breakdown of fats because of the lack of the enzyme alpha galactosidase, fat may accumulate in the walls of the heart, and this will lead to hypertension and cardiac failure
• Decreased perspiration
• Corneal verticillata—clouding of the cornea that does cause problems with the eyesight

Fabry Disease Causes

Fabry disease is caused by the deficiency of the lysosomal enzyme alpha-galactosidase A as evidenced by the mutations in the GLA gene in most of Fabry disease patients. This enzyme is important in the metabolism of lipids and fatlike substances. When this enzyme is lacking or insufficient in the system, lipid breakdown would be incomplete, which will lead to the buildup of fats in areas of the body like the eyes, kidneys, autonomic nervous system as well as the cardiovascular system. This will then cause problems associated with the areas involved.

Fabry Disease Diagnosis

Fabry disease can be life-threatening, so it is very important to diagnose this as early as possible. It is believed that this disease may have started since childhood but is slowly developing. The most striking symptoms that one should take note of are the presence of corneal verticillata (corneal clouding) and angiokeratomas (raised skin blemishes). Furthermore, family history and family members who show similar symptoms are also factors to consider.

In men, they can be diagnosed by testing if the enzyme alpha-galactoside A has deficient activity in plasma, cultured skin fibroblasts, tissue biopsy, or dried blood.

In women, the enzyme’s activity varies from low to normal ranges, so the best way to diagnose them is through mutation analysis if cell mutation has already occurred. Females can be diagnosed with Fabry disease by the absence or how little the activity is of the enzyme alpha-galactoside in the body and the deposition of lipids in the biopsied tissues and urine samples. In addition to this, corneal clouding is also common. Furthermore, Fabry disease can also be diagnosed in the prenatal stage by testing the amniotic fluid and by chorionic villus sampling and amniocentesis.

Fabry Disease Treatment

Treatment of Fabry disease comes from the combined effort from different medical professionals as its symptoms involve multisystem. Also, since not everyone show the same signs and symptoms, it is very important that management should be custom-made for a specific patient.

Pain Management

Neuropathic pain drugs like phenytoin, carbamazepine, and gabapentine are given to patients to reduce the episodes of pain.

GI Symptoms

Although there have not been established treatment to control GI symptoms in patients with Fabry disease, the use of H2 blockers, loperamide, and hydrochloride can relieve GI symptoms.

Skin Symptoms

Laser therapy, combined with enzyme replacement therapy (ERT), has been proven effective in treating skin rashes associated with this disease. It is further believed that the use of liquid nitrogen treatments prior to laser therapy would lead to more desirable results.

Visual Symptoms

Since corneal verticillata do not cause any visual disturbances, visual symptoms in Fabry disease need no treatment.

Enzyme Replacement Therapy (ERT)

The goal of ERT is to reverse the cellular damage and in turn improve symptoms and prevent further disease progression. Based on in-depth clinical studies conducted by medical professionals, the use of ERT as soon as possible after diagnosis would be very beneficial to the patients, especially in male diagnosed patients as well as in female carriers who are showing serious organ system involvement. Instances that warrant female carriers for ERT are as follows:

• Uncontrolled pain that affects quality of life and does not follow age patterns
• Uncontrolled proteinuria
• Patient undergoing dialysis or post organ transplantation
• Cardiac dysfunction and diseases
• Significant brain changes
• Sequential episodes of vertigo
• Severe bouts of fatigue

Based on the research, patients who have been given enzyme replacement therapy have been showing reduced incidence of kidney failure as evidenced by the lower rates of glomerular filtration rate (GFR) decline among diagnosed patients.

In general, ERT is considered tolerable and well recommended treatment for patients with Fabry disease. The most common commercial ERT drugs that are available in market today are Replagal and Fabrazyme have proven effective in many patients to date. With the use of these drugs, evidence-based research shows that there has been, indeed, increased improvement of symptoms in many patients. However, different patients may have different ways of reacting to the drug, depending on the severity of the disease and the extent of damage it had already caused.

The known effects of enzyme replacement therapy are as follows:

• Improved pain symptoms (acroparesthesias) and nerve conduction functions
• Improved skin conditions
• Improved GI symptoms
• Improved perspiration
• Improved renal functions
• Improved cardiac functions