Fabry disease (FD) is an X-linked lysosomal storage disorder due to reduced or undetectable α-galactosidase A (AGAL-A) enzyme activity caused by pathogenic variants in the AGAL-A gene (GLA). Tissue and organ changes are caused by widespread progressive accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3). The classical form of FD is multisystemic with cutaneous (angiokeratomas), neurological (peripheral neuropathy, premature stroke), renal (proteinuria and renal insufficiency), and cardiac involvement. Later onset variants may be limited to the heart. The objective of this review is to summarize the current knowledge on cardiac manifestations of FD and effects of targeted therapy. Cardiac involvement is characterized by progressive hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death (SCD). Targeted therapy is based on enzyme replacement therapy (ERT). Recently, small molecular chaperone, migalastat, became available for patients carrying amenable pathogenic GLA variants. The management of cardiac complications requires a complex approach. Several measures differ from standard clinical guidelines. Betablockers should be used with caution due to bradycardia risk, amiodarone avoided if possible, and anticoagulation used from the first appearance of atrial fibrillation. In Fabry cardiomyopathy SCD calculators are inappropriate. The awareness of FD manifestations is essential for early identification of patients and timely treatment initiation.

• Klíčová slova
• Fabry disease (FD), enzyme replacement therapy (ERT), hypertrophic cardiomyopathy (HCM), molecular chaperones,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The aim of our study was to assess the possible relationships among heme oxygenase (HMOX), bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations, serum bilirubin levels, and Fabry disease (FD). The study included 56 patients with FD (M : F ratio = 0.65) and 185 healthy individuals. Complete standard laboratory and clinical work-up was performed on all subjects, together with the determination of total peroxyl radical-scavenging capacity. The (GT)n and (TA)n dinucleotide variations in the HMOX1 and UGT1A1 gene promoters, respectively, were determined by DNA fragment analysis. Compared to controls, patients with FD had substantially lower serum bilirubin levels (12.0 versus 8.85 μmol/L, p = 0.003) and also total antioxidant capacity (p < 0.05), which showed a close positive relationship with serum bilirubin levels (p = 0.067) and the use of enzyme replacement therapy (p = 0.036). There was no association between HMOX1 gene promoter polymorphism and manifestation of FD. However, the presence of the TA7 allele UGT1A1 gene promoter, responsible for higher systemic bilirubin levels, was associated with a twofold lower risk of manifestation of FD (OR = 0.51, 95% CI = 0.27-0.97, p = 0.038). Markedly lower serum bilirubin levels in FD patients seem to be due to bilirubin consumption during increased oxidative stress, although UGT1A1 promoter gene polymorphism may modify the manifestation of FD as well.

• MeSH
• antioxidancia metabolismus   MeSH
• bilirubin krev   MeSH
• dospělí MeSH
• Fabryho nemoc krev   enzymologie   genetika   MeSH
• glukuronosyltransferasa genetika   MeSH
• hemoxygenasa-1 genetika   MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• promotorové oblasti (genetika) MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• bilirubin MeSH
• glukuronosyltransferasa MeSH
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč
• UGT1A1 enzyme MeSH Prohlížeč