Expert review in diagnostic, therapeutic and follow-up of Fabry disease in Latin America based on patient care standards

Abstract

Background: Fabry disease (FD) is an X-linked lysosomal sphingolipidosis. It is caused by pathogenic variants in the GLA gene with a consequent deficiency of the enzyme α-galactosidase A, resulting in the pathological accumulation of glycolipids - mainly globotriosyl ceramide (GL-3, GB3) and its deacylated product, globotriaosylsphingosine (Lyso-Gb-3) - in plasma and in a wide variety of cell types throughout the human body; it is characterized as a chronic, multisystemic disease with progressive evolution, which causes deterioration of the patient's quality of life and decreases survival and life expectancy.In Latin America there are different limitations to the management of patients with Fabry disease, in most countries, access to diagnostic tools and treatment on time is complex and can sometimes suffer delays in its implementation. This situation is due to the high costs to health systems of follow-up and pharmacological therapy for Fabry patients, creating barriers to timely access. Conclusions: Although medical criteria are fundamental in the choice of pharmacological therapy, the final decision should also rely on the patient's choice according to their expectations and the adherence and compliance with the treatment that they are willing to follow. As it has been described, there are currently three therapeutic options, for which the appropriate profile must be defined to achieve the best clinical outcomes, considering that it is a permanent treatment; experts consider that Fabry patients need comprehensive and interdisciplinary management to stop the progression and functional deterioration of the affected organs by its multiple systemic manifestations. In Latin-American countries, it is difficult to guarantee this comprehensive and coordinated management, due to limited public policies related to orphan diseases diagnosis, treatment and follow up.It is considered crucial to structure support networks specialized in Fabry disease and generate partnerships with health institutions and other health system stakeholders, that would articulate and coordinate patients and relatives counseling and management, establish the specific pharmacological treatment to reduce the progression of the disease and the systemic involvement, deciding between the administration of enzyme replacement therapy or the most recent option of oral management with pharmacological chaperone both with proven effectiveness. This will be the decision of the attending physician, who will propose and advise the therapeutic choice that best suits the patient's needs.

Keywords

• Fabry disease
• Pharmacological chaperone
• Enzyme replacement therapy
• Migalastat
• Alpha-galactosidase a