Topic: Advancements in Diagnosis and Treatment of Fabry Disease 1.0

Fabry disease (FD) is secondary to pathogenic variants of the GLA gene leading to total or partial deficiency of the lysosomal enzyme alpha-galactosidase (AGAL) with the consequence of accumulation of the lipid substrate globotriaosylceramide (Gb3) and its active deacetylated metabolite, globotriaosylsphingosine (Lyso-Gb3). Around 1,000 GLA gene variants have been reported in association with a broad genotype-phenotype correlation with classical and late-onset presentations.

One of the persisting problems over the years is the delayed diagnosis, probably influenced by unspecific early clinical manifestations. The natural course of the disease is a continuum progression where the lysosomal storage leads to a lysosomal dysfunction, cellular damage, and a consequent later organ damage. Early diagnosis relies on biomarkers, but in FD, there is a lack of a definitive biomarker strongly related to the disease burden. Early identification of clinical events, together with biomarkers indicating cellular and organ damage, is crucial to initiating timely and effective treatment. Over the past 20 years, enzyme replacement therapy (ERT) with recombinant AGAL (agalsidase alfa and beta) has been the most extensively utilized treatment. More recently, other therapies such as the chaperone Migalastat and Pegunigalsidase alfa have been approved. Substrate reduction therapy (Lucerastat, Venglustat) is still under clinical trial evaluation, as are some types of genetic therapies. ERT may trigger an immunological reaction, resulting in the production of anti-drug antibodies (ADAs) in a high proportion of patients. Fortunately, personalized and precision treatments are on the horizon for FD patients, though several unmet needs still remain.
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We welcome you to this significant Special Issue on Fabry disease! Our objective is to gather the latest advancements in Diagnosis and Treatment, inviting manuscripts that cover a wide range of relevant topics. Join us as we delve into the ambiguities of GLA gene variant interpretation and unravel the complexities of this condition. Discover the unique clinical characteristics of Pediatric Fabry and explore the diverse perspectives of both male and female patients. Journey through the realm of patient registries and outcome measures, shedding light on the impact of Fabry disease. Gain insights into the varying degrees of severity of Fabry disease, providing a deeper understanding of this condition. Explore the importance of early diagnosis and screening in high-risk populations, extending the scope to include family studies and Newborn Screening (NBS). Uncover the potential of biomarkers such as Lyso-Gb3 and explore new biomarkers that contribute to our knowledge of Fabry disease. Dive into the intricacies of kidney function, albuminuria/proteinuria, and the role of podocytes. Investigate Fabry cardiomyopathy, studying the impact of storage, inflammation, and fibrosis, and utilizing cardiac magnetic resonance imaging for better diagnosis. Explore the connections between Fabry disease, stroke, and transient ischemic attacks (TIA). Gain a deeper understanding of peripheral neuropathy and pain in Fabry disease. Explore the current and future treatment options that hold promise for managing Fabry disease. Lastly, understand the impact of Fabry disease on the quality of life, highlighting the importance of holistic care. Embark on this enlightening journey with us as we uncover new insights and advance our knowledge of Fabry disease for the benefit of patients worldwide.

30 Nov 2023