A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report

BMC Cardiovascular Disorders

Case Report

Antonio Pisani¹  Massimo Imbriaco²  Riccardo Alessandro³  Giuseppe Albeggiani⁴  Francesco Iemolo⁴  Carmela Zizzo⁴  Giovanni Duro⁴  Paolo Colomba⁴ 

[1] Department of Nephrology, University of Naples, Federico II, Italy;Department of Radiology, University of Naples, Federico II, Italy;Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Sezione di Biologia e Genetica, University of Palermo, Palermo, Italy;Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, Via Ugo La Malfa 153, 90146, Palermo, Italy;

关键词: Fabry disease;    α-galactosidase A;    GLA;    Globotriaosylceramide;    High resolution melting;   

DOI  :  10.1186/1471-2261-12-39

 received in 2011-12-20, accepted in 2012-05-21,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundFabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. The incidence of disease is estimated at 1:40,000 in the general population, although neonatal screening initiatives have found an unexpectedly high prevalence of genetic alterations, up to 1:3,100, in newborns in Italy, and have identified a surprisingly high frequency of newborn males with genetic alterations (about 1:1,500) in Taiwan.Case presentationWe describe the case of a 40-year-old female patient who presented with transient ischemic attack (TIA), discomfort in her hands, intolerance to cold and heat, severe angina and palpitations, chronic kidney disease. Clinical, biochemical and molecular studies were performed.ConclusionsReported symptoms, peculiar findings in a renal biopsy – the evidence of occasional lamellar inclusions in podocytes and mesangial cells – and left ventricular (LV) hypertrophy, which are considered to be specific features of FD, as well as molecular evaluations, suggested the diagnosis of a classical form of FD.We detected four mutations in the GLA gene of the patient: -10C>T (g.1170C>T), c.370-77_-81del (g.7188-7192del5), c.640-16A>G (g.10115A>G), c.1000-22C>T (g.10956C>T). These mutations, located in promoter and intronic regulatory regions, have been observed in several patients with manifestations of FD. In our patient clinical picture showed a multisystemic involvement with early onset of symptoms, thus suggesting that these intronic mutations can be found even in patients with classical form of FD.

【 授权许可】

Unknown   
© Pisani et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.