Editorial
Current aspects of Fabry's disease
Aspectos actuales de la enfermedad de Fabry
José-Vicente Torregrosa
Servicio de Nefrología, Hospital Clínic, Barcelona, Spain
Read
4
Timeswas read the article
0
Total PDF
4
Total HTML
Share statistics
array:24 [ "pii" => "S2387020618303085" "issn" => "23870206" "doi" => "10.1016/j.medcle.2018.01.032" "estado" => "S300" "fechaPublicacion" => "2018-09-14" "aid" => "4441" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2018;151:196-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S002577531830085X" "issn" => "00257753" "doi" => "10.1016/j.medcli.2018.01.025" "estado" => "S300" "fechaPublicacion" => "2018-09-14" "aid" => "4441" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2018;151:196-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 34 "formatos" => array:2 [ "HTML" => 17 "PDF" => 17 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Aspectos actuales de la enfermedad de Fabry" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "196" "paginaFinal" => "197" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Current aspects of Fabry's disease" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José-Vicente Torregrosa" "autores" => array:1 [ 0 => array:2 [ "nombre" => "José-Vicente" "apellidos" => "Torregrosa" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020618303085" "doi" => "10.1016/j.medcle.2018.01.032" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618303085?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531830085X?idApp=UINPBA00004N" "url" => "/00257753/0000015100000005/v2_201810230632/S002577531830085X/v2_201810230632/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020618303061" "issn" => "23870206" "doi" => "10.1016/j.medcle.2018.07.005" "estado" => "S300" "fechaPublicacion" => "2018-09-14" "aid" => "4377" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2018;151:198-206" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Direct oral anticoagulants: An update" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "198" "paginaFinal" => "206" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Anticoagulantes orales directos: puesta al día" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2183 "Ancho" => 2294 "Tamanyo" => 306869 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Proposal for the election of direct oral anticoagulants according to subgroups of patients.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">DOAC: direct oral anticoagulants; VKA: vitamin K antagonists; AF: atrial fibrillation.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span>Non-valvular atrial fibrillation is considered atrial fibrillation in the absence of rheumatic mitral stenosis, mechanical or biological valvular prosthesis, or mitral valve repair.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Isabel Franco Moreno, Rosa María Martín Díaz, María José García Navarro" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Ana Isabel" "apellidos" => "Franco Moreno" ] 1 => array:2 [ "nombre" => "Rosa María" "apellidos" => "Martín Díaz" ] 2 => array:2 [ "nombre" => "María José" "apellidos" => "García Navarro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775317309260" "doi" => "10.1016/j.medcli.2017.11.042" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775317309260?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618303061?idApp=UINPBA00004N" "url" => "/23870206/0000015100000005/v1_201810040625/S2387020618303061/v1_201810040625/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2387020618303000" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.11.053" "estado" => "S300" "fechaPublicacion" => "2018-09-14" "aid" => "4364" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2018;151:191-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Lack of association between rheumatoid arthritis and genetic variants rs10889677, rs11209026 and rs2201841 of IL-23R gene" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "191" "paginaFinal" => "195" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Falta de asociación entre la artritis reumatoide y los polimorfismos genéticos rs10889677, rs11209026 y rs2201841 en el gen IL-23R" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Agnieszka Paradowska-Gorycka, Damian Malinowski, Ewa Haladyj, Marzena Olesinska, Krzysztof Safranow, Andrzej Pawlik" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Agnieszka" "apellidos" => "Paradowska-Gorycka" ] 1 => array:2 [ "nombre" => "Damian" "apellidos" => "Malinowski" ] 2 => array:2 [ "nombre" => "Ewa" "apellidos" => "Haladyj" ] 3 => array:2 [ "nombre" => "Marzena" "apellidos" => "Olesinska" ] 4 => array:2 [ "nombre" => "Krzysztof" "apellidos" => "Safranow" ] 5 => array:2 [ "nombre" => "Andrzej" "apellidos" => "Pawlik" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618303000?idApp=UINPBA00004N" "url" => "/23870206/0000015100000005/v1_201810040625/S2387020618303000/v1_201810040625/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Current aspects of Fabry's disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "196" "paginaFinal" => "197" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "José-Vicente Torregrosa" "autores" => array:1 [ 0 => array:3 [ "nombre" => "José-Vicente" "apellidos" => "Torregrosa" "email" => array:1 [ 0 => "vtorre@clinic.ub.es" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Nefrología, Hospital Clínic, Barcelona, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Aspectos actuales de la enfermedad de Fabry" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Fabry disease (FD) is a hereditary metabolic disorder, with a multisystemic, progressive, X-linked inheritance pattern. It is part of a group of diseases called lysosomal storage disorders (LSD), which are characterised by an inadequate deposit of glycolipids in the cellular lysosomes.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> Patients with FD have a deficit or absence of the enzyme alpha-galactosidase (alpha-GAL), due to mutations in the gene that encodes it.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As a result of this deficit, a sphingolipid (globotriaosylceramide or Gb3) accumulates in the body's cells. The deficit of alpha-GAL also causes the accumulation of another related glycolipid, globotriaosylsphingosine (lyso-Gb3), which is the water-soluble, deacetylated form of Gb3, detectable in plasma.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although FD was described at the end of the 19th century, and one might think that everything related to it is sufficiently studied, today there are still many little known or controversial aspects that are subject to open debate. These aspects range from its epidemiology, pathophysiology, and diagnosis, to treatment alternatives.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Historically, the estimated global incidence of FD was considered very low, around one case out of every 117,000–476,000 individuals<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> with an estimated incidence of one in 40,000 males. However, recent data contradict these figures probably due to a previous underestimation due to underdiagnosis of phenotypes with mild manifestations of the disease. Neonatal screening results of various populations reveal that the prevalence can be much higher (estimated at approximately 1/3000)<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> which could turn the FD into an unrecognised pandemic, something perhaps unlikely.</p><p id="par0025" class="elsevierStylePara elsevierViewall">However, in at-risk populations this incidence increases considerably, and thus in recent years an increasing number of screening studies have been carried out in high-risk populations, such as patients with unexplained left ventricular hypertrophy, early stroke patients or patients in dialysis. In these studies, significant differences in prevalence rates have been described, which could also be due, in part, to different laboratory methods and to different cut-off values for screening. At this time in Spain, an ambitious and well-designed screening project is being carried out on patients affected by different stages of chronic kidney disease, and this will, without a doubt, help us to better define its incidence in this at-risk population.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical manifestation of the typical phenotype usually begins in childhood or adolescence and includes disorders in the peripheral nervous system (acroparesthesia), in the skin (angiokeratomas), ocular disorders (corneal verticillata) and progressive renal, heart and central nervous system disorders. There are also phenotypes with less severe involvement, or the so-called atypical variants with involvement of a single organ (cardiac variant or renal variant). It has not been possible to demonstrate a phenotype-genotype correlation, mainly because practically every family presents its own variant and, in addition, there is an enormous variation even among individuals with the same variant.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Clinical involvement is a consequence of the progressive accumulation of Gb3 and lyso-Gb3 molecules. The process by which this accumulation leads to cellular dysfunction and tissue damage is multifactorial and it is currently the subject of controversial theories. In the case of the kidney, it is speculated whether kidney damage could be directly related to its accumulation in podocytes and the subsequent inflammatory process. There are several other factors that seem to play an important role in the pathogenesis of the disease, such as lysosomal damage, vascular involvement in the arterial wall that can lead to haemodynamic changes, and an ATII overregulation,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> oxidative stress, inflammation and fibrosis,<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9,10</span></a> dysfunction of the immune system<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> or the tissue deposition of immune complexes. Therefore, the pathophysiological effects of the accumulation of Gb3 and lyso-Gb3 still need extensive investigation.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnosis of the disease is also an object of debate. After the clinical suspicion of the disease, diagnostic confirmation is made. In the case of males, it is made by enzymatic determination of the alpha-galactosidase and subsequent confirmation by genetic sequencing. Enzymatic determination will show almost undetectable values (<1%) in the case of classical variants while there will be residual activity (>1%) in the case of atypical variants. A further point of controversy is whether the determination should be made in plasma or in leukocytes, since the intracellular traffic is affected in some variants and the intraleukocyte values may be higher than those found in the plasma. In the case of females, the genetic study is mandatory, since the enzymatic activity may be within the range of normality.</p><p id="par0045" class="elsevierStylePara elsevierViewall">More than 800 mutations and numerous polymorphisms related to the <span class="elsevierStyleItalic">GLA gene have been identified worldwide</span>.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> Some patients with “classic” or “severe” phenotypes have mutations that destabilise or cancel the function of the protein, and there are others linked to late or “mild” phenotypes, which are less severe and allow high residual activity to be maintained.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> However, there is much clinical heterogeneity among patients with FD, even among those with the same mutation or in the same family. This seems to show that there is an individual risk to develop complications related to the disease that would depend on interactions between the deficiency of alpha-galactosidase and other factors (genetic, epigenetic or environmental) that should be studied. To date there are very few studies aimed at identifying FD modifying factors.</p><p id="par0050" class="elsevierStylePara elsevierViewall">There is also controversy about possible biomarkers that could facilitate the diagnosis and follow-up of FD. Two specific biomarkers for FD are postulated: Gb3 and lyso-Gb3.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> Elevated Gb3 levels are used as a biomarker for both diagnosis and treatment. However, it is a very poor indicator of the disease progression and its response to treatment.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> Plasma values of lyso-Gb3 correlate with the severity of the disease. They are detectable at a very early age and can help to differentiate the classical forms of FD from the variants (high values would confirm the diagnosis in patients with variants of uncertain significance). However, in females, the high values of lyso-Gb3 would indicate FD, but the normal values would not exclude the disease.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> On the other hand, the plasmatic values of lyso-Gb3 seem to reduce with the enzymatic replacement treatment, but this decrease does not correlate with the evolution of the disease.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Nowadays, in addition to the symptomatic treatment of the manifestations associated with FD, there is also enzyme replacement therapy (ERT), which has been available for more than 17 years, and which compensates for the enzyme deficiency causing the disease. Additionally, there is treatment with chaperones available for the short term. Chaperones are small molecules designed to improve residual enzymatic activity and that protect the mutated enzyme against intracellular degradation.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Regarding treatment, the controversy focuses on 2 fundamental aspects: when to start treatment and which drug to administer.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The appropriate time to initiate or discontinue enzyme replacement therapy remains undefined, especially in certain groups of patients, such as in the case of young males between 5 and 16 years of age or in male patients with moderate renal disease (GFR <45<span class="elsevierStyleHsp" style=""></span>ml/min<span class="elsevierStyleHsp" style=""></span>1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>). There is also an open debate about which early signs should be considered as susceptible for the start of treatment, such as podocyte substrate deposits.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Therefore, it seems necessary to look for new biomarkers of involvement, as well as progress predictors, that will facilitate the long-term follow-up of patients.</p><p id="par0070" class="elsevierStylePara elsevierViewall">On the other hand, new and old controversies persist regarding the 2 ERTs existing in the European market: agalsidase alpha (Replagal; Shire Human Genetic Therapies AB, Danderyd, Sweden) and agalsidase β (Fabrazyme; Genzyme Corporation, Cambridge, MA, USA), as they question the differences in efficacy of the different doses approved for the treatment of FD: 0.2<span class="elsevierStyleHsp" style=""></span>mg/kg every 2 weeks and 1<span class="elsevierStyleHsp" style=""></span>mg/kg every 2 weeks, respectively.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The differences inherent in their different production mechanisms (human cell line in the case of agalsidase alpha and Chinese Hamster Ovary cell line in the case of agalsidase β) lead to different molecular structures, which, by definition, makes them non-identical and with different dose regimens.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Although it has been speculated that the difference in dose could lead to differences in efficacy, to date no studies have been conducted with the primary objective of directly comparing both ERTs, and it is difficult to establish differences based on isolated data from the efficacy studies. A recent Cochrane systematic review that compiled all the studies conducted with agalsidase α and β concluded that, at the approved doses, no superiority of one treatment over the other was objectified.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In summary, although the knowledge of FD has increased considerably in recent years, especially since the advent of enzyme replacement therapy, we still have many doubts to resolve, including its epidemiology, physiopathology, clinical correlation, factors that can condition the wide range of clinical manifestations, what biomarkers can help us both for the diagnosis and to assess the evolution of the disease or the treatment response, as well as when is the appropriate time to start the enzyme replacement therapy or the future alternatives.</p><p id="par0090" class="elsevierStylePara elsevierViewall">So we still have a large number of challenges ahead of us regarding the management of this disorder that require studies that cover as wide a scope as possible to find answers.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Torregrosa J-V. Aspectos actuales de la enfermedad de Fabry. Med Clin (Barc). 2018;151:196–197.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Online Mendelian Inheritance in Man. Fabry disease (301500). Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.omim.org/entry/301500?-search=301500%26highlight=301500">http://www.omim.org/entry/301500?-search=301500&highlight=301500</a> [accessed 26.09.17]." ] ] ] 1 => array:3 [ "identificador" => "bib0110" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.D. MacDermot" 1 => "A. Holmes" 2 => "A.H. Miners" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2001" "volumen" => "38" "paginaInicial" => "750" "paginaFinal" => "760" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11694547" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0115" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[Chapter 2]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of lysosomal storage diseases: an overview" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Fuller" 1 => "P.J. Meikle" 2 => "J.J. Hopwood" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Fabry disease: perspectives from 5 years of FOS" "serieFecha" => "2006" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0120" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High incidence of later-onset Fabry disease revealed by newborn screening" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Spada" 1 => "S. Pagliardini" 2 => "M. Yasuda" 3 => "T. Tukel" 4 => "G. Thiagarajan" 5 => "H. Sakuraba" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/504601" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2006" "volumen" => "79" "paginaInicial" => "31" "paginaFinal" => "40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16773563" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0125" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PrEFiNe plan: strategic plan for Fabry diseases in nephrology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Pino" 1 => "A. Ortiz" 2 => "R. Torra" 3 => "D. Hernandez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.nefro.2016.03.009" "Revista" => array:6 [ "tituloSerie" => "Nefrologia" "fecha" => "2016" "volumen" => "36" "paginaInicial" => "376" "paginaFinal" => "380" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27118193" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0130" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "α-galactosidase alactosidase a deficiency: Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.J. Desnick" 1 => "J.A. Ioannou" 2 => "C.M. Eng" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:6 [ "titulo" => "The metabolic and molecular bases of inherited disease" "fecha" => "2001" "paginaInicial" => "3733" "paginaFinal" => "3774" "editorial" => "McGraw Hill" "editorialLocalizacion" => "Nueva York" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0135" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Mehta" 1 => "R. Ricci" 2 => "U. Widmer" 3 => "F. Dehout" 4 => "A. Garcia de Lorenzo" 5 => "C. Kampmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2362.2004.01309.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Invest" "fecha" => "2004" "volumen" => "34" "paginaInicial" => "236" "paginaFinal" => "242" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15025684" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0140" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Copious podocyturia without proteinuria and with normal renal function in a young adult with Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Trimarchi" 1 => "R. Canzonieri" 2 => "A. Muryan" 3 => "A. Schiel" 4 => "A. Araoz" 5 => "M. Forrester" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2015/257628" "Revista" => array:5 [ "tituloSerie" => "Case Rep Nephrol" "fecha" => "2015" "volumen" => "2015" "paginaInicial" => "257628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26064721" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0145" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.B. Biancini" 1 => "C.S. Vanzin" 2 => "D.B. Rodrigues" 3 => "M. Deon" 4 => "G.S. Ribas" 5 => "A.G. Barshak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbadis.2011.11.001" "Revista" => array:6 [ "tituloSerie" => "Biochim Biophys Acta" "fecha" => "2012" "volumen" => "1822" "paginaInicial" => "226" "paginaFinal" => "232" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22085605" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0150" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fibrosis: a key feature of Fabry disease with potential therapeutic implications" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Weidemann" 1 => "M.D. Sanchez-Niño" 2 => "J. Politei" 3 => "J.P. Oliveira" 4 => "C. Wanner" 5 => "D.G. Warnock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1750-1172-8-116" "Revista" => array:5 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "116" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23915644" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0155" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune system irregularities in lysosomal storage disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.A. Castaneda" 1 => "M.J. Lim" 2 => "J.D. Cooper" 3 => "D.A. Pearce" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00401-007-0296-4" "Revista" => array:6 [ "tituloSerie" => "Acta Neuropathol" "fecha" => "2008" "volumen" => "115" "paginaInicial" => "159" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17924126" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0160" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The molecular defect leading to Fabry disease: structure of human α-galactosidase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.C. Garman" 1 => "D.N. Garboczi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jmb.2004.01.035" "Revista" => array:6 [ "tituloSerie" => "J Mol Biol" "fecha" => "2004" "volumen" => "337" "paginaInicial" => "319" "paginaFinal" => "335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15003450" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0165" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.M. Aerts" 1 => "W.W. Kallemeijn" 2 => "W. Wegdam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10545-011-9308-6" "Revista" => array:6 [ "tituloSerie" => "J Inherit Metab Dis" "fecha" => "2011" "volumen" => "34" "paginaInicial" => "605" "paginaFinal" => "619" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21445610" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0170" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Vedder" 1 => "G.E. Linthorst" 2 => "M. van Breemen" 3 => "J.E. Groener" 4 => "F.J. Bemelman" 5 => "A. Strijland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10545-006-0484-8" "Revista" => array:6 [ "tituloSerie" => "J Inherit Metab Dis" "fecha" => "2007" "volumen" => "30" "paginaInicial" => "68" "paginaFinal" => "78" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17206462" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0175" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma globotriaosylsphingosine in relation to phenotypes of Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B.E. Smid" 1 => "L. van der Tol" 2 => "M. Biegstraaten" 3 => "G.E. Linthorst" 4 => "C.E. Hollak" 5 => "B.J. Poorthuis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmedgenet-2014-102872" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2015" "volumen" => "52" "paginaInicial" => "262" "paginaFinal" => "268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25596309" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0180" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Biegstraaten" 1 => "R. Arngrímsson" 2 => "F. Barbey" 3 => "L. Boks" 4 => "F. Cecchi" 5 => "P.B. Deegan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13023-015-0253-6" "Revista" => array:5 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25885911" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0185" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Hughes" 1 => "K. Nicholls" 2 => "S.P. Shankar" 3 => "G. Sunder-Plassmann" 4 => "D. Koeller" 5 => "K. Need" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmedgenet-2016-104178" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2017" "volumen" => "54" "paginaInicial" => "288" "paginaFinal" => "296" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27834756" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0190" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Available from: <a id="intr0015" class="elsevierStyleInterRef" href="http://www.ema.europa.eu/docs/es_ES/WC500053612.pdf">www.ema.europa.eu/docs/es_ES/document_library/../WC500053612.pdf</a> [accessed 25.03.17]." ] ] ] 18 => array:3 [ "identificador" => "bib0195" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Lee" 1 => "X. Jin" 2 => "K. Zhang" 3 => "L. Andrews" 4 => "J. Baker-Malcolm" 5 => "L. Geagan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/glycob/cwg034" "Revista" => array:6 [ "tituloSerie" => "Glycobiology" "fecha" => "2003" "volumen" => "13" "paginaInicial" => "305" "paginaFinal" => "313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12626384" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0200" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enzyme replacement therapy for Anderson-Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. El Dib" 1 => "H. Gomaa" 2 => "R.P. Carvalho" 3 => "S.E. Camargo" 4 => "R. Bazan" 5 => "P. Barretti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/14651858.CD006663.pub4" "Revista" => array:5 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2016" "volumen" => "7" "paginaInicial" => "CD006663" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27454104" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015100000005/v1_201810040625/S2387020618303085/v1_201810040625/en/main.assets" "Apartado" => array:4 [ "identificador" => "46797" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorial article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015100000005/v1_201810040625/S2387020618303085/v1_201810040625/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618303085?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 June | 1 | 0 | 1 |
| 2023 March | 2 | 0 | 2 |
| 2019 January | 1 | 0 | 1 |
