Fabry disease: where are we now?

Area of Science:

• Genetics and Genetic Diseases
• Biochemistry
• Nephrology

Background:

• Fabry disease (FD) is a lysosomal storage disorder caused by alpha-galactosidase deficiency.
• This X-linked condition leads to globotriaosylceramide (Gb3) accumulation, affecting multiple organs.
• While typically more severe in males, females can also present with disease manifestations.

Purpose of the Study:

• To provide a comprehensive review of Fabry disease (FD) focusing on nephropathy.
• To discuss the prevalence, clinical and genetic characteristics, pathophysiology, and diagnostic methods for FD-related kidney disease.
• To outline current and emerging therapeutic strategies for managing FD nephropathy.

Main Methods:

• Literature review of scientific articles and clinical studies on Fabry disease and nephropathy.
• Synthesis of information regarding FD genetics, pathophysiology, diagnosis, and treatment options.
• Analysis of current therapeutic approaches, including enzyme replacement therapy (ERT) and novel treatments.

Main Results:

• FD is characterized by Gb3 accumulation due to alpha-galactosidase deficiency, impacting various organs, including kidneys.
• Diagnostic approaches involve enzyme activity assays, Gb3 level measurements, and genetic testing.
• Current treatments include ERT, with emerging options like chaperone therapy, substrate reduction therapy, and gene therapy.

Conclusions:

• Fabry disease poses a significant risk for kidney damage, necessitating early diagnosis and intervention.
• Effective management of FD nephropathy relies on a combination of established and novel therapeutic strategies.
• Continued research into FD pathophysiology and treatment is crucial for improving patient outcomes.