Septal Myectomy in Patients with Hypertrophic Cardiomyopathy and Nonclassical Anderson-Fabry Disease.

Anderson-Fabry disease (AFD) results from decreased enzyme activity of lysosomal enzymes and intralysosomal storage of nonhydrolyzed forms. Cardiovascular complications, mainly in the form of HCM, contribute substantially to AFD patient mortality. Here, we report three new cases of obstructive HCM (HOCM) in nonclassical presentations of AFD and isolated cardiac involvement. In all three cases, the diagnosis of AFD was made postoperatively by routine genetic and morphological testing. Together with previously published cases, this report illustrates the potential safety and beneficial effect of septal surgical myectomy in patients with AFD-HOCM, as well as underlines the need for more thorough screening for clinical signs of AFD-associated cardiomyopathy and GLA variants among patients with HOCM.

Case Report: Two New Cases of Autosomal-Recessive Hypertrophic Cardiomyopathy Associated With TRIM63-Compound Heterozygous Variant.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary diseases, and it is associated with fatal complications. The clinical heterogeneity of HCM requires risk prediction models to identify patients at a high risk of adverse events. Most HCM cases are caused by mutations in genes encoding sarcomere proteins. However, HCM is associated with rare genetic variants with limited data about its clinical course and prognosis, and existing risk prediction models are not validated for such patients' cohorts. TRIM63 is one of the rare genes recently described as a cause of HCM with autosomal-recessive inheritance. Herein, we present two cases of HCM associated with TRIM63-compound heterozygous variants in young male sportsmen. They demonstrated progressively marked hypertrophy, advanced diastolic dysfunction, a significant degree of fibrosis detected by magnetic resonance imaging, and clear indications for implantable cardioverter-defibrillator. One of the cases includes the first description of TRIM63-HCM with extreme hypertrophy. The presented cases are discussed in light of molecular consequences that might underlie cardiac and muscle phenotype in patients with mutations of TRIM63, the master regulator of striated muscle mass.