Fabry disease cardiomyopathy: A state-of-the-art review

Fabry disease or Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (GLA), leading to systemic accumulation of globotriaosyl-ceramide (Gb3). Initially described in 1898 as a dermatological condition, Fabry disease is now recognized as a progressive multisystem disorder with significant cardiac involvement. Cardiomyopathy in Fabry disease arises from Gb3 accumulation in cardiac tissue, resulting in fibrosis, left ventricular hypertrophy (LVH), diastolic dysfunction, and heart failure. The deacylated derivative, lysoGb3, serves as a biomarker of cardiac involvement. Diagnosis relies on enzyme assays, genetic testing, and advanced cardiac imaging modalities like echocardiography and cardiac MRI. Management strategies are centered around enzyme replacement therapy, and prognosis varies due to phenotypic heterogeneity and severity of disease progression. Psychological and social burdens further complicate patient care. However, underdiagnosis remains a concerning issue, particularly in individuals with unexplained cardiomyopathies. Early recognition through increased clinical awareness and genetic screening is crucial for timely intervention. Ongoing research is essential to develop new therapies targeting the genetic and metabolic roots of the disease. This systematic review comprehensively examines current evidence regarding the mechanisms, diagnosis, treatment, and prognosis of cardiomyopathy associated with Fabry disease, providing insights that may enhance clinical practice and guide future research initiatives.