title: Fabry disease presenting as apical left ventricular hypertrophy in a patient carrying the missense mutation R118C.
abstract: Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by abnormalities of the GLA gene, which encodes the enzyme α-galactosidase A. A deficiency of this enzyme leads to the lysosomal accumulation of glycosphingolipids, which may cause left ventricular hypertrophy that is typically concentric and symmetric. We present the case of a 60-year-old woman with symptoms of dyspnea, atypical chest pain and palpitations, in whom a transthoracic echocardiogram revealed an apical variant of hypertrophic cardiomyopathy. Analysis of specific sarcomeric genetic mutations was negative. The patient underwent a screening protocol for Anderson-Fabry disease, using a dried blood spot test, which was standard at our institution for patients with left ventricular hypertrophy. The enzymatic activity assay revealed reduced α-galactosidase A enzymatic activity. Molecular analysis identified a missense point mutation in the GLA gene (p.R118C). This case report shows that Anderson-Fabry disease may cause an apical form of left ventricular hypertrophy. The diagnosis was only achieved because of systematic screening, which highlights the importance of screening for Anderson-Fabry disease in patients with unexplained left ventricular hypertrophy, including those presenting with more unusual patterns, such as apical variants of left ventricular hypertrophy. This case also supports the idea that the missense mutation R118C is indeed a true pathogenic mutation of Anderson-Fabry disease.
authors.affiliation: Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. Electronic address: franciscacaetano@sapo.pt.
authors.forename: Francisca
authors.initials: F
authors.lastname: Caetano
authors.affiliation: Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Botelho
authors.affiliation: Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Mota
authors.affiliation: Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Silva
authors.affiliation: Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Leitão Marques
mesh_terms: D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D008875:Middle Aged; D020125:Mutation, Missense; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase
keywords: Anderson-Fabry disease; Apical hypertrophic cardiomyopathy; Doença de Anderson-Fabry; Echocardiography; Ecocardiograma; Genetics; Genética; Miocardiopatia hipertrófica apical; Rastreio; Screening