Fabry Disease Treatments

Fabry disease is a genetic lysosomal storage disease that progresses with age and cannot be cured. The disease is caused by a deficiency in the enzyme α-galactosidase A, which leads to a build up in cells of a glycolipid called globotriaosylceramide (also called ceramide trihexoside or Gb3 or GL-3). This glycolipid gets deposited in the blood vessels, tissues and organs, eventually disrupting their function.

In the past, the main aim of treatment has been to ease the patient’s symptoms as much as possible to improve their quality of life and prolong their lifespan. Today, the condition is treated by replacing the enzyme that is deficient using enzyme replacement therapy (ERT).

Two ERTs are currently available and these include:

• Agalsidase alpha (Replagal, manufactured by Shire)
• Agalsidase beta (Fabrazyme, manufactured by Genzyme).

Each of these agents is administered every two weeks by intravenous injection. The treatment is very expensive and cost an estimated US$200,000 per patient in 2012, a price that is unaffordable to most individuals. Although ERT cannot provide a cure for patients with Fabry disease, it can improve metabolism, help to prevent disease progression, and possibly reverse some symptoms.

Aside from treating the disease itself, the management of Fabry disease is focused on treating the associated complications such as cardiovascular, renal and gastrointestinal problems, hearing loss and skin symptoms.

The associated symptoms of Fabry disease are managed as follows:

Pain and neuropathic pain

The pain felt in Fabry disease is often debilitating and does not respond to standard pain relief medications. Examples of medications that may be beneficial include carbamazepine, oxcarbazepin, gabapentin, phenytoin and pregabalin.

Gastrointestinal symptoms

The gastrointestinal symptoms are similar to those seen in irritable bowel syndrome such as vomiting, nausea and diarrhea. These symptoms can be controlled using an antiemetic such as metoclopramide and planning the frequency of meals consumed.

Skin symptoms

The small dark spots (angiokeratomas) that typically affect the skin can cause discomfort and even bleeding. These lesions can be removed using laser treatment.

Hearing loss

The hearing loss that occurs in Fabry disease is usually gradual but can also occur quite suddenly. A hearing aid may be required to restore hearing ability. Tinnitus is another common hearing disorder among these patients.

Kidney function

Kidney damage also occurs gradually in Fabry disease and treatment will depend on how far the damage has progressed. Medications that may be prescribed to improve kidney function include angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). If kidney function has been lost altogether, then dialysis may be required.

Stroke

Ischemic stroke is more common among people with Fabry disease compared with the general population and anticoagulant medications may be prescribed to help reduce the risk of stroke occurring.