GI-tract pain is likely caused by accumulation of lipids in the small vasculature of the GI tract, which obstructs blood flow and causes pain. Kidney
Kidney complications are common and serious effects of the disease; chronic kidney disease and kidney failure may worsen throughout life. The presence of protein in the urine (which causes foamy urine) is often the first sign of kidney involvement. End-stage kidney failure in those with Fabry disease typically occurs in the third decade of life, and is a common cause of death due to the disease. Heart
Fabry disease can affect the heart in several ways. The accumulation of sphingolipids within heart muscle cells causes abnormal thickening of the heart muscle or hypertrophy. This hypertrophy can cause the heart muscle to become abnormally stiff and unable to relax, leading to a restrictive cardiomyopathy causing shortness of breath.Fabry disease can also affect the way in which the heart conducts electrical impulses, leading to both abnormally slow heart rhythms such as complete heart block, and abnormally rapid heart rhythms such as ventricular tachycardia. These abnormal heart rhythms can cause blackouts, palpitations, or even sudden cardiac death.Sphingolipids can also build up within the heart valves, thickening the valves and affecting the way they open and close. If severe, this can cause the valves to leak (regurgitation) or to restrict the forward flow of blood (stenosis). The aortic and mitral valves are more commonly affected than the valves on the right side of the heart.
Late gadolinium enhancement shows increased signal of the midwall at the inferolateral wall of the base of the left ventricle, usually in the non-hypertrophic ventricle. T1-weighted imaging can show low T1 signal due to sphingolipid storage in the heart even without ventricular hypertrophy in 40% of the those affected by the disease. Thus, MRI is a useful way of diagnosing the disease early. T2 signal is increased in inflammation and oedema. Treatment
The treatments available for Fabry disease can be divided into therapies that aim to correct the underlying problem of decreased activity of the alpha galactosidase A enzyme and thereby reduce the risk of organ damage, and therapies to improve symptoms and life expectancy once organ damage has already occurred. Therapies targeting enzyme activity
Enzyme replacement therapy is designed to provide the enzyme the patient is missing as a result of a genetic malfunction. This treatment is not a cure, but can partially prevent disease progression, and potentially reverse some symptoms. As of March 2022, two medical drugs based on enzyme replacement therapy are available for Fabry disease:
Agalsidase alfa, sold under the brand name Replagal by the company Takeda (since its acquisition of the company Shire), is a recombinant form of alpha-galactosidase A It received approval in the EU in 2001. FDA approval was applied for the United States. However, Shire withdrew their application for approval in the United States in 2012, citing that the agency will require additional clinical trials before approval. As of March 2022, Replagal has not received FDA approval.