Medications for Fabry Disease

Fabry disease is an inherited condition (runs in families) that is caused by a mutation or defect in a gene called the GLA gene (also called the Fabry gene) located on the X chromosome.

A person with Fabry’s disease is unable to make enough of an enzyme called alpha-galactosidase A (or alpha-GAL) that is responsible for breaking down and clearing a fatty substance called globotriaosylceramide or GL-3. As a result, Gl-3 accumulates in various tissues in the body such as the kidneys, heart, and skin, and can cause symptoms such as mini-strokes, marble-like patterning in the eyes, hearing loss, heart disease, digestive problems, skin changes, an inability to sweat, or temperature sensitivity. Left untreated, Fabry disease can reduce life expectancy by 15 years in women and 20 years in men.

What are the symptoms of Fabry disease?

Symptoms of Fabry disease are caused by the build-up of GL-3 which starts to build up before birth and continues throughout a person’s life. Symptoms can vary depending on how old the person is, how severe their disease is, the activity of their enzymes, or their type of genetic variation. Symptoms may include:

Chest pain
Corneal whirling (marble-like patterns in the eyes)
Digestive problems, such as diarrhea, abdominal pain, early satiety (feeling full after only a little food), and nausea
Kidney disease
Hearing loss
Heart disease
Inability to sweat
Ministrokes or transient ischemic attacks (TIAs)
Pain in the hands or the feet
Reddish or purple spots on the skin
Temperature sensitivity
Tinnitus.

Some symptoms may worsen with time without the person noticing. Left untreated, Fabry disease can reduce life expectancy by 15 years in women and 20 years in men.

How is Fabry disease diagnosed?

Genetic testing for the GLA gene is the most reliable and informative method for diagnosing Fabry disease in both males and females. This uses cells from a sample of blood or saliva to look for disease-causing mutations in the GLA gene. Males and females only have to inherit one mutated GLA gene copy to develop the disease.

In male patients, enzyme tests, which measure the activity of alpha-GAL in the blood, may be used to diagnose Fabry disease in males. Levels of less than 1% of normal are typical of classic, more severe, Fabry disease. Levels above 1% but lower than the normal range suggest a late-onset, milder form. The activity of Alpha-GAL is often within the normal range in female patients limiting the usefulness of these tests, and genetic tests should be used to diagnose females and confirm the diagnosis in males.

Some states also offer newborn screening for Fabry disease. This involves collecting a blood spot from a heel prick and analyzing the levels of Gal A activity.

Enzyme and genetic testing also can be done before birth to see if an unborn baby has a disease-causing GLA mutation. This may be done at about 10 weeks of pregnancy, using a placenta sample or by analyzing the liquid surrounding the fetus at about 15 weeks (just past three months) of gestation.

A test for Lyso-Gb3, another fatty substance that accumulates in the blood or the urine as a result of Gal A deficiency, may be used to diagnose Fabry disease, particularly in female patients.

After a diagnosis of Fabry disease has been established, other tests such as echocardiograms, electrocardiograms, brain and heart MRI scans, and blood tests may be used to determine what organs are affected.

Fabry disease is frequently misdiagnosed because symptoms of the condition can be very nonspecific (such as gastrointestinal complaints such as abdominal pain or diarrhea) especially those that present early in life, and many healthcare providers are unfamiliar with the disease. The full range of symptoms of Fabry disease may not present until adulthood.

How many people have Fabry disease and how is it passed on?

Fabry disease affects people of all ages and ethnicities and traditionally has been thought to be very rare, affecting up to 1 in 40,000 to 50,000 males, with an unknown prevalence in women because they tend to be carriers with no or nonsignificant symptoms.

However, the true incidence of Fabry disease is likely to be much higher, because newborn screening studies in some countries identified the condition in 1 in 3400–4000 newborns. The National Fabry Disease Foundation estimates 50,000 people in the U.S. carry the Fabry gene, many of whom remain undiagnosed or misdiagnosed with other conditions.

On average, five family members are diagnosed with Fabry disease for every patient identified. Testing family members can help diagnose cases of Fabry disease early before serious problems arise, as well as identify girls and women who carry a mutated GLA copy but have no symptoms (called carriers). These women can pass it to their children, especially boys since males only have one X chromosome (inherited from the mother) and thereby will develop the more severe disease when inheriting a mutated gene. In females who inherit two X chromosomes, one from the mother and one from the father, the presence of a healthy gene copy can compensate for the mutated copy to a certain extent.

Men with Fabry disease will transmit the GLA mutation to all their daughters, who typically will develop the disease, but not to a son, because boys receive a Y sex chromosome from their fathers, instead of an X chromosome. Most female patients who carry only one mutated GLA gene copy will have a 50% chance of passing the mutated gene to each of their children, both daughters, and sons.

How is Fabry disease treated?

There is no cure for Fabry disease but treatments can help replace the missing alpha-GAL enzyme, restore alpha-GAL activity, prevent organ damage, and ease symptoms. Treatments include:

Enzyme replacement therapies such as Fabrazyme
Chaperone therapies such as Galafold.
Other treatments such as dialysis or kidney transplants.

References

Fabrazyme (agalsidase beta) [Product information]. Updated 03/2021. Sanofi Genzyme https://www.drugs.com/pro/fabrazyme.html
Fabrazyme. Fabrazyme.com 2021.
Zar-Kessler C, Karaa A, Sims KB, Clarke V, Kuo B. Understanding the gastrointestinal manifestations of Fabry disease: promoting prompt diagnosis. Therap Adv Gastroenterol. 2016;9(4):626-634. doi:10.1177/1756283X16642936
Diagnosis of Fabry Disease. Fabry Disease News. 2021 https://fabrydiseasenews.com/diagnosis-of-fabry-disease/

Drugs used to treat Fabry Disease

The following list of medications are in some way related to or used in the treatment of this condition.

Drug name	Rating	Reviews	Rx/OTC	Pregnancy	CSA
Fabrazyme	Rate	Add review	Rx	B	N
Generic name: agalsidase beta systemic Drug class: lysosomal enzymes For consumers: dosage, interactions, side effects For professionals: Prescribing Information

Galafold	Rate	Add review	Rx		N
Generic name: migalastat systemic Drug class: miscellaneous metabolic agents For consumers: dosage, interactions, side effects For professionals: Prescribing Information

agalsidase beta	Rate	Add review	Rx	B	N
Generic name: agalsidase beta systemic Brand name: Fabrazyme Drug class: lysosomal enzymes For consumers: dosage, interactions, side effects For professionals: AHFS DI Monograph

migalastat	Rate	Add review	Rx		N
Generic name: migalastat systemic Brand name: Galafold Drug class: miscellaneous metabolic agents For consumers: dosage, interactions, side effects For professionals: AHFS DI Monograph

Legend

Rating	For ratings, users were asked how effective they found the medicine while considering positive/adverse effects and ease of use (1 = not effective, 10 = most effective).
Activity	Activity is based on recent site visitor activity relative to other medications in the list.
Rx	Prescription only.
OTC	Over-the-counter.
Rx/OTC	Prescription or Over-the-counter.
Off-label	This medication may not be approved by the FDA for the treatment of this condition.
EUA	An Emergency Use Authorization (EUA) allows the FDA to authorize unapproved medical products or unapproved uses of approved medical products to be used in a declared public health emergency when there are no adequate, approved, and available alternatives.

Pregnancy Category
A	Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
B	Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
C	Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use in pregnant women despite potential risks.
D	There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use in pregnant women despite potential risks.
X	Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use in pregnant women clearly outweigh potential benefits.
N	FDA has not classified the drug.

Controlled Substances Act (CSA) Schedule
M	The drug has multiple schedules. The schedule may depend on the exact dosage form or strength of the medication.
U	CSA Schedule is unknown.
N	Is not subject to the Controlled Substances Act.
1	Has a high potential for abuse. Has no currently accepted medical use in treatment in the United States. There is a lack of accepted safety for use under medical supervision.
2	Has a high potential for abuse. Has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. Abuse may lead to severe psychological or physical dependence.
3	Has a potential for abuse less than those in schedules 1 and 2. Has a currently accepted medical use in treatment in the United States. Abuse may lead to moderate or low physical dependence or high psychological dependence.
4	Has a low potential for abuse relative to those in schedule 3. It has a currently accepted medical use in treatment in the United States. Abuse may lead to limited physical dependence or psychological dependence relative to those in schedule 3.
5	Has a low potential for abuse relative to those in schedule 4. Has a currently accepted medical use in treatment in the United States. Abuse may lead to limited physical dependence or psychological dependence relative to those in schedule 4.

Alcohol
X	Interacts with Alcohol.

Further information

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