Diagnostic, Treatment Options for Fabry Disease Summarized in Review

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A recent review has summarized the current diagnostic tools and available treatments for Fabry disease,  highlighting the challenges and potential new avenues to improve patients’ diagnoses and clinical outcomes.

The review, “Diagnosis and Treatment of the Cardiovascular Consequences of Fabry Disease” was published in the QJM: An International Journal of Medicine.

Fabry disease is a rare genetic disorder that prevents the body from making an enzyme called alpha-galactosidase A. This enzyme is responsible for breaking down a type of fat called globotriaosylceramide (Gb3 or GL-3) into building blocks that the body’s cells can use.

When these fat molecules are not broken down due to lack of alpha-galactosidase, they build up inside the cells and cause damage.

Since it was first recognized, the diagnosis of Fabry has been challenging, especially because some patients exhibit milder forms of the disease that manifest only later in life.

An early diagnosis has been increasingly recognized as necessary, specifically focusing on early detection of organ involvement and disease progression.

Most patients identified through genetic screening lack the classical signs of the disease, like heat intolerance, opaque corneas, or a burning or tingling sensation in body the hands and feet.

However, they often involve the cardiac system. Late presentation in some patients has led to the concept of a “cardiac variant,” specifically left ventricular hypertrophy (LVH), a condition in which the left part of the heart chamber has thickened and does not pump blood in an efficient manner.


Several diagnostic methods are available and represent a valuable asset when diagnosing LVH and other cardiac variants in Fabry patients.

For example, heart structural and functional changes can be diagnosed through an electrocardiogram (ECG), an exam that evaluates the electric activity of the heart.

Transthoracic echocardiography (TTE) — still or moving images of the internal parts of the heart using ultrasound — also can be a useful method to detect LVH. Because many patients do not have LVH at the time of diagnosis, however, standard echocardiography has limitations in diagnosing cardiac involvement.

Cardiovascular magnetic resonance imaging (CMR), a medical imaging technology that can evaluate cardiac function in a non-invasive manner, is widely used to assess structural disease and characterization of cardiac involvement, and may aid in Fabry patients’ diagnosis.

Cardiac variants in Fabry patients can have an impact in effort tolerance, and when combined with exercise, can help with a diagnostic. Enzyme replacement therapy, when initiated early, may preserve exercise capacity, although it does not improve effort intolerance for those in whom cardiac involvement, namely myocardial fibrosis, has already developed.

Myocardial perfusion imaging and coronary angiography are imaging techniques that also have shown  promise to facilitate the early detection of cardiac involvement in Fabry disease.

Several cardiac biomarkers can help detect the presence of cardiac involvement in Fabry disease.

Specifically, troponin (a protein involved in muscle contraction)  and NT-proBNP) a substance produced in the heart) may precede LVH and can support the presence of cardiac involvement in these patients, while correlating with disease severity.


Some treatment options are currently available. Despite a lack of studies showing benefits, classical recommendations include smoking cessation and increasing physical activity. In addition, maintaining a strict blood pressure can contribute to a delay in the progression of LVH in Fabry patients.

Certain medications, such as beta-blockers or calcium-channel blockers (to manage abnormal heart rhythm) should be taken with caution and close monitoring due to increased risk of conduction disease and bradycardia in these patients.

Patients also can undergo enzyme replacement therapy (ERT), which is mainly directed at replacing the deficient or absent GAL-A enzyme. The therapy is administered via intravenous infusions and available sources include agalsidase beta (Fabrazyme, developed by Sanofi-Genzyme) and agalsidase alpha (Replagal, developed by Shire).

Galafold (migalastat), developed by Amicus Therapeutics, is a newer orally available small molecule pharmacological chaperone that can binds to the active site of the GAL-A enzyme, stabilizing specific forms of the mutant enzyme.

Cardiac transplantation also is considered a viable option for patients who have a severe, life-limiting heat disease. However, the presence of renal dysfunction frequently can impair organ acceptance.

[Cardiovascular] disease is the most frequent cause of death in [Fabry disease] and has a major impact on quality of life. Clinical presentation is variable, and symptoms do not always correlate with extent of disease. As such a combination of clinical, biochemical and imaging features are crucial in correctly identifying patients with cardiac involvement, assessing severity and determining treatment,” the authors wrote.

“Novel imaging and blood biomarkers are emerging that enable earlier diagnosis, opening a potential window for early therapy at which time the inevitable cascade of irreversible cardiovascular damage may be potentially averted,” they concluded.