Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder from a mutation in the alpha-galactosidase A (GLA) gene, with absolute or partial GLA deficiency causing accumulation of glycosphingolipids in various organs. The causative pathogenic mutation (classical vs late onset) plays a significant role in the resultant phenotype. Due to the X-linked inheritance, males have more severe and earlier disease manifestations (~10 years earlier than in females). Accumulation in the heart begins in utero and continues throughout life. In addition to the direct accumulation of glycosphingolipids, inflammatory injury contributes to increased ventricular wall thickness and ultimately fibrosis. A gender-based dimorphism may also exist, with males demonstrating a more marked hypertrophic response to myocyte injury.

The most common cardiac manifestation is increased left ventricular (LV) wall thickness; however, this is preceded by decades of subclinical organ involvement. While overt echocardiographic changes are reported in the third or fourth decade, abnormalities on ECG and cardiac magnetic resonance (CMR) imaging (reduced native T1 time) occur earlier, reflecting prolonged ‘pre-hypertrophic’ cardiac disease. Echocardiographic strain imaging also detects early cardiac involvement, with reductions in global longitudinal strain (GLS) observed prior to the development of increased LV wall thickness.1

Commencement of disease-modifying enzyme replacement therapy (ERT) or oral chaperone therapy is based on the causative GLA mutation, gender and the presence of overt clinical disease. Treatment stabilises or even causes regression of cardiac disease and is more effective started early in the disease course.

Monda and colleagues2 performed a retrospective, observational cohort …