Answers to questions families often have about caring for their child with Fabry disease

Fabry disease is an inherited condition that runs in families. It is caused by a mutation in the GLA gene located on the X chromosome. The GLA gene contains the instructions needed to make the α-galactosidase A enzyme. This enzyme normally breaks down a particular fatty substance, globotriaosylceramide or GL-3, in the body's cells. Without a sufficient amount of GL-3 enzyme, GL-3 progressively accumulates in cells throughout the body, especially in the lining of blood vessels, the heart, nervous system, and kidneys causing damage.

Some people with Fabry disease have a mutation in the GLA gene that results in the absence of the enzyme, and they may have a more severe or “classic” form of the disease. Others with Fabry disease may have a mutation that results in a decreased amount of the enzyme or a form of the enzyme that does not work as well. This may cause a milder form of the disease.

Other names for Fabry disease are Alpha-Galactosidase A Deficiency and Anderson-Fabry Disease.

Fabry disease affects many different parts of the body. Symptoms often begin in childhood and may include:

• Frequent burning or tingling pain in the hands and feet
• Episodes of severe pain that usually begin in the hands and feet and spread to other parts of the body, often when a child has a fever or is overheated (Fabry “crisis”)
• Little or no sweating (hypohydrosis/anhydrosis)
• Gastrointestinal problems include abdominal pain, diarrhea/constipation, nausea, vomiting, and bloating
• A non-itchy rash consisting of groups of small, dark red spots on the skin (angiokeratomas)
• A whorling (spiral) pattern in the cornea of the eye found during an eye exam that does not affect vision (cornea verticillata)
• Ringing in the ears (tinnitus) and/or hearing loss
• Fatigue (tiredness)

For males, a diagnosis of Fabry disease can usually be made based on the results of tests that measure the amount of α-galactosidase A enzyme in the blood. Females with Fabry may have normal or near-normal enzyme levels in the blood and still have Fabry disease. Females usually need to have the diagnosis confirmed by looking at the GLA gene on the X chromosome. This can be done with blood or saliva.

Renal, cardiovascular, or cerebrovascular complications can limit the lifespan of those with Fabry disease. If untreated, males have a life expectancy of approximately 50 years; females have a life expectancy of 70 years. This represents a reduction of at least 20 and 10 years, respectively. A child’s quality of life and participation in home and school activities may be impacted by symptoms such as pain and gastrointestinal disturbances.

Fabry disease follows an X-linked inheritance pattern. So, if a man has Fabry disease, he will pass the disease on to all of his daughters and none of his sons. If a woman has Fabry disease, each child born to her has a 50% chance of having the disease.

Since Fabry disease runs in families, other family members need to understand the risks. This includes parents, siblings, cousins, aunts, and uncles in your immediate and extended family. Consultation with a genetic counselor is recommended to help build a genetic family tree and determine each individual’s risks.

There is currently no cure for Fabry disease. Treatment is focused on halting or slowing the progression of the disease and managing symptoms. The only medication approved specifically for Fabry disease in the United States is agalsidase-beta (Fabrazyme). This medication is an enzyme replacement therapy (ERT) and a manufactured version of the enzyme lacking in Fabry disease. Fabrazyme is given by infusion through an IV every 2 weeks.

Other medications may be used to help control pain, including carbamazepine, gabapentin, phenytoin, and analgesics. H2 blockers and metoclopramide have been used to help with GI problems. Many other medications and therapies may be prescribed to help with renal or cardiac issues.

Fabry symptoms vary greatly; some children may have few symptoms, while others may have severe presentations that significantly affect the family. Support groups can be a great source of information and assist in navigating the challenges of this disease.

Some organizations (listed in Resources below) can help families finance their child's treatment.

There are many organs affected by Fabry disease, including the heart. More individuals with Fabry disease die from heart-related complications than from kidney damage. Both the heart and the kidneys should be closely monitored.

No, because of X-inactivation, females can have a large range of symptoms. Some females may be as affected as males, while some may not have symptoms. Females with Fabry disease need to be monitored and treated appropriately.