Anderson-Fabry disease: a multiorgan disease

Area of Science:

• Genetics
• Biochemistry
• Pathology

Background:

• Fabry disease (FD) is an X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency.
• Glycolipid accumulation, primarily globotriaosylceramide (Gb3), in vascular endothelium leads to inflammation and fibrosis.
• FD presents with diverse phenotypes, affecting organs like kidneys, heart, and brain, with renal failure being a serious complication.

Purpose of the Study:

• To summarize the clinical manifestations, pathophysiology, and diagnostic challenges of Fabry disease.
• To highlight the importance of early diagnosis and timely intervention, particularly for Fabry nephropathy.
• To discuss the spectrum of disease progression and management strategies.

Main Methods:

• Review of existing literature on Fabry disease.
• Analysis of clinical presentations, including organ-specific involvement.
• Discussion of diagnostic criteria and biomarkers.

Main Results:

• FD exhibits a wide spectrum of clinical phenotypes, affecting multiple organ systems.
• Fabry nephropathy can progress silently in childhood, necessitating early detection.
• Challenges in diagnosing FD, especially in children and female heterozygotes, are noted.
• Vascular dysfunction, endothelial dysfunction, and a pro-thrombotic state contribute to FD pathophysiology.
• Cardiac and neurological manifestations are significant, including hypertrophy, valvulopathy, and cerebrovascular disease.

Conclusions:

• Fabry disease requires a comprehensive understanding of its varied clinical course and pathophysiology.
• Early diagnosis and intervention are critical to prevent irreversible organ damage, particularly renal failure.
• Improved diagnostic tools and biomarkers are needed for timely detection and management of FD.