BMC Cardiovascular Disorders | |
A classical phenotype of Anderson-Fabry disease in a female patient with intronic mutations of the GLA gene: a case report | |
Giovanni Duro3  Francesco Iemolo3  Riccardo Alessandro1  Paolo Colomba3  Giuseppe Albeggiani3  Carmela Zizzo3  Massimo Imbriaco2  Antonio Pisani4  | |
[1] Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Sezione di Biologia e Genetica, University of Palermo, Palermo, Italy;Department of Radiology, University of Naples, Federico II, Italy;Institute of Biomedicine and Molecular Immunology “A. Monroy”, National Research Council, Via Ugo La Malfa 153, 90146, Palermo, Italy;Department of Nephrology, University of Naples, Federico II, Italy | |
关键词: High resolution melting; Globotriaosylceramide; GLA; α-galactosidase A; Fabry disease; | |
Others : 1084949 DOI : 10.1186/1471-2261-12-39 |
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received in 2011-12-20, accepted in 2012-05-21, 发布年份 2012 | |
【 摘 要 】
Background
Fabry 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 presentation
We 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.
Conclusions
Reported 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】
2012 Pisani et al.; licensee BioMed Central Ltd.
【 预 览 】
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Figure 1. | 45KB | Image | download |
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