Dostalova, G.; Januska, J.; Veselá, M.; Reková, P.; Taborska, A.; Pleva, M.; Zemanek, D.; Linhart, A. Anderson–Fabry Disease Homozygosity: Rare Case of Late-Onset Variant. Cardiogenetics2024, 14, 74-83.
Dostalova, G.; Januska, J.; Veselá, M.; Reková, P.; Taborska, A.; Pleva, M.; Zemanek, D.; Linhart, A. Anderson–Fabry Disease Homozygosity: Rare Case of Late-Onset Variant. Cardiogenetics 2024, 14, 74-83.
Dostalova, G.; Januska, J.; Veselá, M.; Reková, P.; Taborska, A.; Pleva, M.; Zemanek, D.; Linhart, A. Anderson–Fabry Disease Homozygosity: Rare Case of Late-Onset Variant. Cardiogenetics2024, 14, 74-83.
Dostalova, G.; Januska, J.; Veselá, M.; Reková, P.; Taborska, A.; Pleva, M.; Zemanek, D.; Linhart, A. Anderson–Fabry Disease Homozygosity: Rare Case of Late-Onset Variant. Cardiogenetics 2024, 14, 74-83.
Abstract
Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients.
Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access.
Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.
Keywords
Anderson - Fabry disease; homozygosity; exon 5; late onset
Subject
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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