Abstract

Fabry disease (FD) is an X-linked lysosomal disorder caused by pathogenic variants in the GLA gene encoding the enzyme α-galactosidase A (α-Gal A). Male patients with classic FD have severely reduced or absent α-Gal A activity, resulting in the accumulation of globotriaosylceramide in a variety of tissues. This causes early and progressive damage to the targeted organs, life-threatening complications, and an increased risk of premature death. The severity of the disease is more variable in females because of random X chromosome inactivation and its impact on α-Gal A activity. The definition of appropriate timing of treatment initiation is crucial in classic FD patients, notably in the pediatric population, as the clinically asymptomatic progression of renal, cardiac and cerebral manifestations spans many years.

Today, the key question is whether the state-of-the-art knowledge of Fabry, the available treatment options and the current physicians' experiences make it necessary to develop a new paradigm in the therapeutic management of patients with classic FD. To answer this question, the authors reviewed a selection of papers specifically reporting the results of enzyme replacement therapy in classic FD patients.

In the published literature, the authors highlight how the introduction of a new paradigm in the management of pediatric patients with classic FD is now possible through the definition of the appropriate treatment regimen and timing of treatment.

A Delphi panel on Early Treatment in pediatric classic Fabry Disease, under the aegis of the Italian Society for the Study of Inherited Metabolic Diseases and Newborn Screening (SIMMESN), is working on these novel approaches. The theoretical assumptions underlying the resulting consensus, that will be available in another publication, are reported here.