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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La enfermedad de Fabry &#40;EF&#44; OMIM 301500&#41; es una enfermedad por dep&#243;sito lisosomal &#40;EDL&#41;&#46; Este grupo de enfermedades incluye al menos 50 entidades hereditarias de baja frecuencia&#44; originadas por un error cong&#233;nito del metabolismo secundario a un defecto monog&#233;nico espec&#237;fico que conduce a la deficiencia en la actividad de una enzima lisosomal<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">1</span></a>&#46; Dicha deficiencia produce el ac&#250;mulo de sustratos no metabolizados primariamente en los lisosomas y luego&#44; progresivamente&#44; en otros compartimientos celulares<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">1&#44;2</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">En la EF&#44; la actividad ausente o deficiente de la enzima<span class="elsevierStyleHsp" style=""></span>&#945;-galactosidasa-A &#40;&#945;-gal-A&#44; EC 3&#46;2&#46;1&#46;22&#41; produce la acumulaci&#243;n multisist&#233;mica de glicoesfingol&#237;pidos complejos&#44; principalmente globotriaosilceramida &#40;Gb3&#41;&#44; desde etapas fetales de la vida<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">La incidencia reportada de la EF se encuentra en el rango de un caso por cada 476&#46;000 a un caso por cada 117&#46;000 nacidos vivos en la poblaci&#243;n general<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#44; aunque cribados neonatales en Italia y Taiw&#225;n han reportado resultados mayores<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; Los estudios de prevalencia en poblaciones susceptibles informan valores de 0&#44;33&#37; en varones y de 0&#44;1&#37; en mujeres con enfermedad renal cr&#243;nica terminal &#40;ERCT&#41; de etiolog&#237;a desconocida<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">El dep&#243;sito anormal de sustrato no metabolizado afecta pr&#225;cticamente a todos los tejidos y &#243;rganos de la econom&#237;a&#44; pero es m&#225;s predominante en el endotelio y en las c&#233;lulas musculares lisas de los vasos sangu&#237;neos&#44; junto con las c&#233;lulas epiteliales renales&#44; los cardiomiocitos y las c&#233;lulas neurales<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46; Como consecuencia del almacenamiento lisosomal de Gb3 se desencadena una cascada de fen&#243;menos delet&#233;reos&#44; entre los que se encuentran el compromiso del metabolismo energ&#233;tico&#44; la lesi&#243;n de peque&#241;os vasos&#44; la disfunci&#243;n de canales i&#243;nicos en c&#233;lulas endoteliales&#44; el aumento del estr&#233;s oxidativo&#44; las alteraciones de la autofagia&#44; la isquemia y su resultado final&#44; la fibrosis tisular<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">La globotriaocilesfingosina &#40;Lyso-Gb3&#41;&#44; producto del metabolismo anormal de Gb3&#44; se encuentra elevada en pacientes con EF&#46; Entre sus efectos conocidos se reconocen&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>inhibici&#243;n de la actividad enzim&#225;tica &#945;-gal-A&#59; b&#41;<span class="elsevierStyleHsp" style=""></span>liberaci&#243;n local de mediadores qu&#237;micos de da&#241;o glomerular&#44; y c&#41;<span class="elsevierStyleHsp" style=""></span>inducci&#243;n de proliferaci&#243;n vascular&#44; con engrosamiento del complejo &#237;ntima-media arterial<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">7-9</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">En el ri&#241;&#243;n&#44; los dep&#243;sitos progresivos de Gb3 afectan c&#233;lulas tubulares&#44; glomerulares &#40;incluidos los podocitos&#41;&#44; endoteliales y musculares lisas vasculares&#46; Esto ha sido demostrado en biopsias renales de pacientes aun sin manifestaciones cl&#237;nicas de compromiso renal<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">10&#44;11</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Los primeros s&#237;ntomas de la EF se expresan durante la ni&#241;ez&#44; con acroparestesias&#44; crisis de dolor neurop&#225;tico en los cuatro miembros&#44; hipohidrosis&#44; dolor abdominal recurrente&#44; diarrea&#44; n&#225;useas y saciedad precoz&#44; asociados a angioqueratomas&#46; Durante la adolescencia se agregan c&#243;rnea verticilada&#44; manifestaciones disauton&#243;micas y disminuci&#243;n de la capacidad auditiva&#46; Llegada la adultez&#44; se desarrolla enfermedad renal&#44; card&#237;aca y cerebrovascular&#44; con morbimortalidad aumentada y disminuci&#243;n de la expectativa de vida comparada con la poblaci&#243;n general<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Hasta el a&#241;o 2001 se describi&#243; el fallo renal como la principal causa de muerte en la EF<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">12</span></a>&#46; Posteriormente se report&#243; que la principal causa de muerte es la cardiovascular &#40;57&#37; de los casos&#41;&#44; que los pacientes que mueren por causa cardiovascular hab&#237;an recibido previamente terapia dial&#237;tica y hab&#237;an sido diagnosticados en forma tard&#237;a<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">13</span></a>&#46; Por esta raz&#243;n&#44; la investigaci&#243;n de la nefropat&#237;a en los pacientes con EF&#44; sus mecanismos&#44; evoluci&#243;n y tratamiento&#44; ha sido un tema de relevancia entre expertos<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">14-20</span></a>&#46; Dentro de ese campo de investigaci&#243;n&#44; la detecci&#243;n temprana de la nefropat&#237;a ha sido de inter&#233;s&#44; debido a que los tratamientos espec&#237;ficos para la EF son m&#225;s eficaces en estadios precoces de da&#241;o renal&#44; disminuyendo su eficacia en etapas avanzadas&#44; principalmente debido al desarrollo de fibrosis tisular<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">6&#44;21</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">La evaluaci&#243;n de la nefropat&#237;a por EF ha sido estudiada por biomarcadores tanto moleculares como tisulares<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">17&#44;22-24</span></a>&#44; que poseen ventajas y desventajas para su utilizaci&#243;n en la pr&#225;ctica habitual&#59; ente las &#250;ltimas&#44; la escasa accesibilidad de los m&#233;todos de alta complejidad en algunas &#225;reas geogr&#225;ficas y las complicaciones de los m&#233;todos invasivos dificultan su uso rutinario<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">25</span></a>&#46; El prop&#243;sito del presente trabajo es describir el rol del especialista en nefrolog&#237;a en el diagn&#243;stico temprano de la EF y las variables cl&#237;nicas asociadas a nefropat&#237;a en pacientes afectados&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><p id="par0050" class="elsevierStylePara elsevierViewall">Dise&#241;o transversal con recolecci&#243;n de datos retrospectivos&#46; Datos preliminares del presente estudio han sido previamente publicados<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">26</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">El estudio fue aprobado por cada comit&#233; de &#233;tica local&#46; Los pacientes mayores de edad&#44; con criterios de inclusi&#243;n&#44; firmaron el consentimiento informado&#46; Los menores de edad dieron su asentimiento&#44; y firm&#243; el consentimiento informado su tutor o representante legal de acuerdo con la normativa local&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Se reclutaron pacientes con diagn&#243;stico probable de EF desde junio de 2007 a septiembre de 2017 de tres centros de referencia en Argentina&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>Centro de Neurociencias Los Manantiales&#44; Grupo Gamma Rosario&#44; Rosario&#44; Provincia de Santa Fe&#59; b&#41;<span class="elsevierStyleHsp" style=""></span>Centro de Infusi&#243;n y Estudio de Enfermedades Lisosomales del Instituto de Nefrolog&#237;a Cl&#237;nica Pergamino&#44; Pergamino&#44; Provincia de Buenos Aires&#44; y c&#41;<span class="elsevierStyleHsp" style=""></span>Servicio de Terapia Intensiva del Hospital Dr&#46; Enrique Erill de Escobar&#44; Bel&#233;n de Escobar&#44; Provincia de Buenos Aires&#46; Se incluyeron pacientes con diagn&#243;stico confirmado de EF por estudio gen&#233;tico y dosaje enzim&#225;tico &#945;-gal-A&#46; Criterios de exclusi&#243;n&#58; pacientes con nefropat&#237;a de otra etiolog&#237;a diferente a la EF&#46; Criterios de eliminaci&#243;n&#58; pacientes con criterio de inclusi&#243;n que se nieguen a participar del estudio o que presenten alguna complicaci&#243;n relacionada con la extracci&#243;n de sangre o con la realizaci&#243;n de estudios diagn&#243;sticos durante su realizaci&#243;n&#46; Las mutaciones patog&#233;nicas del gen GLA fueron detectadas por estudio gen&#233;tico&#44; mediante secuenciaci&#243;n directa y <span class="elsevierStyleItalic">Multiplex ligation-dependent probe amplification</span> &#40;MLPA&#41;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">27&#44;28</span></a>&#46; El dosaje de actividad &#945;-gal-A se realiz&#243; por m&#233;todo fluorom&#233;trico<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">29</span></a>&#44; y se consider&#243; normal o disminuido por encima y por debajo de 4&#44;0<span class="elsevierStyleHsp" style=""></span>nmol&#47;h&#47;l&#44; respectivamente&#46; La creatinina en plasma y orina fue determinada por electro-quimio-luminiscencia Roche Diagnostics&#46; El FGe se calcul&#243; con ecuaci&#243;n de Schwartz y el CKD-EPI en pacientes menores y mayores de 21<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; respectivamente<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">30&#44;31</span></a>&#46; Para estadificar el FGe se utiliz&#243; la clasificaci&#243;n <span class="elsevierStyleItalic">Kidney Disease&#58; Improving Global Outcomes Chronic Kidney Disease Guideline 2013</span> &#40;KDIGO&#41;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">32</span></a>&#46; La albuminuria fue determinada por m&#233;todo colorim&#233;trico Roche Diagnostics<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a>&#46; El cociente alb&#250;mina&#47;creatinina en orina fue utilizado para estimar la excreci&#243;n urinaria de prote&#237;nas en 24<span class="elsevierStyleHsp" style=""></span>h&#46; Valores de 0 a 30 fueron considerados normales&#44; de 30 a 300 microalbuminuria y mayor a 300 albuminuria&#44; en al menos dos muestras de orina<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a>&#46; La nefropat&#237;a en adultos se defini&#243; por&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>microalbuminuria o albuminuria&#44; y&#47;o b&#41;<span class="elsevierStyleHsp" style=""></span>FGe menor a 90<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; y&#47;o c&#41;<span class="elsevierStyleHsp" style=""></span>antecedente de requerimiento de terapia de reemplazo de funci&#243;n renal mediante di&#225;lisis o trasplante&#46; La nefropat&#237;a en pacientes pedi&#225;tricos se defini&#243; por la presencia de excreci&#243;n urinaria de prote&#237;nas aumentada &#40;microalbuminuria o albuminuria&#41;&#59; no se consideraron los cambios del FGe por las limitaciones que posee el c&#225;lculo del FGe con f&#243;rmulas que utilizan creatinina en pacientes pedi&#225;tricos<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">34</span></a>&#46; Se determin&#243; la proporci&#243;n de casos &#237;ndices diagnosticados por un especialista en nefrolog&#237;a&#46; Se utilizaron las definiciones cl&#225;sicas de factores de riesgo cardiovascular<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a>&#46; El compromiso del sistema nervioso perif&#233;rico &#40;SNP&#41; fue considerado por la presencia de dolor neurop&#225;tico t&#237;pico de EF o alteraciones de la prueba <span class="elsevierStyleItalic">Quantitative sensory testing</span> &#40;QST&#41;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a>&#46; El compromiso digestivo fue determinado por la presencia de dolor abdominal&#44; diarrea recurrente&#44; n&#225;useas o saciedad precoz en relaci&#243;n con ingesta copiosa sin otra causa distinta a la EF<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;37</span></a>&#46; La c&#243;rnea verticilata fue evaluada mediante examen oftalmol&#243;gico con l&#225;mpara de hendidura<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;38</span></a>&#46; Los angioqueratomas fueron evaluados por un dermat&#243;logo especialista en EF<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46; Las alteraciones auditivas fueron evaluadas por logo-audiometr&#237;a<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46; El compromiso card&#237;aco fue diferenciado en&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>arritmias&#44; y b&#41;<span class="elsevierStyleHsp" style=""></span>cardiopat&#237;a estructural&#44; por presentarse ambas alteraciones en la edad pedi&#225;trica y adulta&#44; de manera diferencial&#44; en los pacientes afectados&#46; Las arritmias se definieron por la presencia de alteraciones electrofisiol&#243;gicas en electrocardiograma &#40;ECG&#41; de 12 derivaciones&#46; La cardiopat&#237;a estructural se defini&#243; por la presencia de hipertrofia del VI en ecocardiograma doppler color y&#47;o im&#225;genes t&#237;picas en resonancia nuclear magn&#233;tica &#40;RMN&#41; card&#237;aca con gadolinio<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;39</span></a>&#46; El compromiso del sistema nervioso central &#40;SNC&#41; de defini&#243; por el antecedente de Stroke y&#47;o im&#225;genes t&#237;picas en RMN cerebral asintom&#225;ticas<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;40</span></a>&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lisis estad&#237;stico</span><p id="par0065" class="elsevierStylePara elsevierViewall">Variable dependiente&#58; nefropat&#237;a&#46; Variables independientes&#58; sexo&#44; edad&#44; actividad &#945;-gal-A&#44; compromiso del SNP&#44; compromiso gastrointestinal&#44; c&#243;rnea verticilata&#44; angioqueratomas&#44; alteraciones auditivas&#44; arritmias&#44; cardiopat&#237;a estructural&#44; compromiso del SNC&#44; hipertensi&#243;n arterial &#40;HTA&#41; y tabaquismo&#46; Se calcul&#243; el odds ratio para las dos variables consideradas factores de riesgo de nefropat&#237;a en los pacientes con EF&#58; actividad &#945;-gal-A&#44; HTA<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">15&#44;41</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Los datos fueron procesados en una base SPSS Statistics 20&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Para determinar la asociaci&#243;n entre la variable dependiente y las independientes &#40;variables nominales&#41; se utiliz&#243; la prueba de chi-cuadrado con datos organizados en tablas de contingencia&#46; No se utiliz&#243; factor de correcci&#243;n de Yates por contar con una muestra mayor a 40&#44; ni test exacto de Fisher por frecuencias esperadas mayor a 5&#46; Se trabaj&#243; con intervalo de confianza del 95&#37;&#46; Para el c&#225;lculo de p se utiliz&#243; la tabla de distribuci&#243;n de chi-cuadrado seg&#250;n grado de libertad&#46; Valores de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 fueron considerados de significaci&#243;n estad&#237;stica para rechazar la hip&#243;tesis nula &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0080" class="elsevierStylePara elsevierViewall">Se estudiaron 72 pacientes con diagn&#243;stico confirmado de EF &#40;26&#44;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;482<span class="elsevierStyleHsp" style=""></span>a&#241;os&#41;&#44; 30 &#40;41&#44;6&#37;&#41; varones y 42 &#40;58&#44;4&#37;&#41; mujeres&#46; Se incluyeron 27 &#40;37&#44;5&#37;&#41; pacientes pedi&#225;tricos y 45 &#40;62&#44;5&#37;&#41; adultos&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Fueron encontrados 13 genotipos&#58; E398X&#44; L415P&#44; M296V&#44; L106R&#44; R227Q&#44; A292T&#44; c&#46;448&#46;delG&#44; R363H&#44; C382Y&#44; R301Q&#44; D109G&#44; del 3&#38;4 exons&#44; W81X&#44; todas mutaciones patog&#233;nicas del gen GLA&#46; Se estudiaron 14 pacientes &#171;caso &#237;ndice&#187;&#58; 12 hombres y 2 mujeres&#44; todos adultos&#46; El 50&#37; de los mismos fueron diagnosticados por un especialista en nefrolog&#237;a&#44; el 14&#44;5&#37; por un cardi&#243;logo&#44; el 14&#44;5&#37; por un dermat&#243;logo&#44; y los restantes&#44; el 7&#37; por cada especialidad&#58; neurolog&#237;a&#44; reumatolog&#237;a y genetista&#46; La distribuci&#243;n de frecuencias se muestra en la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46; De los 12 casos &#237;ndices varones&#44; 11 pacientes presentaron da&#241;o renal &#40;5 pacientes con ERCT&#41;&#46; Las dos mujeres caso &#237;ndice no presentaron da&#241;o renal&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">La totalidad de los casos &#237;ndice presentaron el fenotipo cl&#225;sico de la enfermedad&#44; habi&#233;ndose encontrado las manifestaciones tempranas t&#237;picas de la infancia en el 100&#37; de los mismos&#46; La prevalencia de eventos mayores t&#237;picos de la edad adulta en la EF en el grupo casos &#237;ndice fue la siguiente&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>un paciente &#40;6&#44;00&#37;&#41; present&#243; un evento mayor&#59; b&#41;<span class="elsevierStyleHsp" style=""></span>7 pacientes &#40;46&#44;6&#37;&#41; presentaron dos eventos mayores&#44; y c&#41;<span class="elsevierStyleHsp" style=""></span>6 pacientes &#40;40&#44;0&#37;&#41; presentaron tres eventos mayores&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Se hall&#243; nefropat&#237;a en 44 pacientes &#40;61&#44;1&#37;&#41;&#58; 6 pedi&#225;tricos y 38 adultos&#46; La media de FGe en la poblaci&#243;n pedi&#225;trica fue 115&#44;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#44;87<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; y en adultos&#44; 80&#44;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#44;22<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; La <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a> muestra la distribuci&#243;n de frecuencias de nefropat&#237;a seg&#250;n el estadio KDIGO&#46; El 100&#37; de los pacientes en estadios G3&#44; G4 y G5 fueron varones&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">El tabaquismo y la HTA fueron los &#250;nicos factores de riesgo cardiovascular presentes en la poblaci&#243;n estudiada&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se analiza si existe una relaci&#243;n significativa entre los pacientes con o sin nefropat&#237;a &#40;variable dependiente&#41; y una serie de variables cl&#237;nicas descriptivas &#40;independientes&#41;&#46; La <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> muestra los valores de odds ratio calculados para los factores de exposici&#243;n para la variable dependiente &#40;nefropat&#237;a&#41;&#58; &#945;-gal-A disminuida&#44; HTA y tabaquismo&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discusi&#243;n</span><p id="par0110" class="elsevierStylePara elsevierViewall">La nefropat&#237;a es una de las complicaciones mayores en la EF<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">26</span></a>&#46; Se caracteriza por proteinuria y disminuci&#243;n progresiva del FGe<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;26</span></a>&#46; La disminuci&#243;n del FGe a trav&#233;s del tiempo se encuentra en relaci&#243;n directa al grado de proteinuria y&#44; sin intervenci&#243;n terap&#233;utica&#44; es m&#225;s pronunciada en pacientes con FGe inicial menor a 60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span><a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">15</span></a>&#46; En nuestra poblaci&#243;n&#44; el 18&#37; de los pacientes presentaron FGe menor a 60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> al momento del diagn&#243;stico&#46; La HTA y el sexo masculino han sido descriptos como factores de riesgo de nefropat&#237;a en los pacientes con EF<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Por la progresi&#243;n de la nefropat&#237;a por EF&#44; los varones afectados presentan ERCT con requerimiento de terapias de reemplazo de funci&#243;n renal a la edad media de 42<span class="elsevierStyleHsp" style=""></span>a&#241;os<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a>&#44; dato que coincide con la edad de ingreso a di&#225;lisis de todos nuestros pacientes con ERCT estudiados&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En la nefropat&#237;a por EF se asume que el da&#241;o inicial es producido por el dep&#243;sito anormal de sustrato no metabolizado&#44; Gb3 y sus metabolitos<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;20</span></a>&#46; Esto conduce a una cascada de fen&#243;menos que incluyen el compromiso del metabolismo energ&#233;tico&#44; la lesi&#243;n de peque&#241;os vasos&#44; la disfunci&#243;n de canales i&#243;nicos en c&#233;lulas endoteliales&#44; el aumento del estr&#233;s oxidativo&#44; las alteraciones de la autofagia&#44; la isquemia y su resultado final&#44; la fibrosis tisular<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;6&#44;20</span></a>&#46; Lyso-Gb3&#44; el principal metabolito de Gb3&#44; a las concentraciones plasm&#225;ticas encontradas en los pacientes con EF induce TGF-&#946;1 autocrina y se&#241;ales Notch-1 en los podocitos&#44; de manera similar a la respuesta podocitaria a las concentraciones elevadas de glucosa<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">8&#44;42</span></a>&#44; v&#237;as que tambi&#233;n conducen a fibrosis renal<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">La terapia de reemplazo enzim&#225;tico es el &#250;nico tratamiento espec&#237;fico para la EF que ha demostrado revertir la acumulaci&#243;n tisular de Gb3 en tejido renal&#44; incluidos los podocitos&#44; aunque de manera dosis-dependiente<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">43</span></a>&#46; Su eficacia es mayor cuanto m&#225;s tempranamente se inicie&#44; debido a la imposibilidad de corregir la progresi&#243;n cuando se encuentran presentes lesiones irreversibles&#44; como la fibrosis tisular<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">6&#44;21&#44;44</span></a>&#46; Chaperonas farmacol&#243;gicas han demostrado cambios histol&#243;gicos significativos en c&#233;lulas intersticiales capilares&#44; pero no as&#237; en podocitos<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">45</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">La fibrosis renal ha sido demostrada en pacientes con funci&#243;n renal normal y sin albuminuria<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">10&#44;11&#44;16</span></a>&#44; y se han estudiado biomarcadores en etapas prealbumin&#250;ricas de la nefropat&#237;a por EF&#44; tanto moleculares como histol&#243;gicos<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">8&#44;10&#44;11&#44;16&#44;17&#44;22-24</span></a>&#46; La alta complejidad y el costo de ciertos m&#233;todos no invasivos y las complicaciones de los procedimientos invasivos dificultan su uso rutinario en la pr&#225;ctica habitual&#44; por lo que planteamos un modelo capaz de predecir con validez la asociaci&#243;n entre variables cl&#237;nicas asociadas a nefropat&#237;a y que ayude al m&#233;dico asistencial en la detecci&#243;n temprana del da&#241;o renal en los pacientes afectados&#44; mediante la simple asociaci&#243;n de datos cl&#237;nicos&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">En la evoluci&#243;n natural de la EF el dep&#243;sito tisular multisist&#233;mico de Gb3 se produce de manera progresiva<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46; Este concepto coincide con los resultados encontrados en nuestro estudio&#44; en el que hubo significaci&#243;n estad&#237;stica entre nefropat&#237;a y la edad de los pacientes&#46; En las primeras etapas del da&#241;o tisular los pacientes permanecen asintom&#225;ticos&#44; hasta que los dep&#243;sitos de sustrato y la lesi&#243;n tisular alcanzan un nivel cr&#237;tico y se producen manifestaciones cl&#237;nicas por disfunci&#243;n org&#225;nica<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a>&#46; Dos tipos de variables cl&#237;nicas se asociaron con significaci&#243;n estad&#237;stica a nefropat&#237;a en nuestros pacientes&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>compromiso del SNP&#44; angioqueratomas y compromiso auditivo&#44; manifestaciones cl&#237;nicas del fenotipo cl&#225;sico &#40;m&#225;s severo&#41; de la EF&#44; y por otro lado&#44; b&#41;<span class="elsevierStyleHsp" style=""></span>cardiopat&#237;a estructural y el compromiso del SNC&#44; que son complicaciones mayores&#44; junto a nefropat&#237;a en los pacientes adultos afectados&#44; responsables de la morbimortalidad aumentada y la menor expectativa de vida&#46; Ambos tipos de variables no son manifestaciones tempranas en los pacientes con EF&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="par0140" class="elsevierStylePara elsevierViewall">Los varones con EF presentan nefropat&#237;a avanzada al momento del diagn&#243;stico&#44; y el especialista en nefrolog&#237;a cumple un rol de importancia en el mismo&#46; No hubo diagn&#243;sticos de caso &#237;ndice en etapas pedi&#225;tricas&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Como se demuestra en este estudio&#44; la asociaci&#243;n de manifestaciones cl&#237;nicas como variables de relaci&#243;n con nefropat&#237;a podr&#237;a significar el reconocimiento en etapas tard&#237;as del da&#241;o renal&#46; Parecer&#237;a razonable continuar en la b&#250;squeda de biomarcadores capaces de diagnosticar nefropat&#237;a en etapas precoces&#44; lo cual lograr&#237;a modificar eficazmente el pron&#243;stico de los pacientes afectados por esta enfermedad&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicto de intereses</span><p id="par0150" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de inter&#233;s relacionados con el contenido del trabajo enviado&#46;</p></span></span>"
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              "titulo" => "Background"
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              "titulo" => "An&#225;lisis estad&#237;stico"
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    "fechaRecibido" => "2018-01-16"
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          "palabras" => array:4 [
            0 => "Enfermedad de Fabry"
            1 => "Nefropat&#237;a"
            2 => "Proteinuria"
            3 => "Diagn&#243;stico temprano"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Fabry disease"
            1 => "Nephropathy"
            2 => "Proteinuria"
            3 => "Early diagnosis"
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    "resumen" => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La detecci&#243;n temprana de la nefropat&#237;a por enfermedad de Fabry es de inter&#233;s&#44; pues su tratamiento es m&#225;s eficaz en estadios precoces&#46; Ha sido estudiada por biomarcadores moleculares y tisulares&#44; pero estos poseen desventajas que dificultan su uso rutinario&#46; El prop&#243;sito del presente trabajo es describir el rol del nefr&#243;logo en el diagn&#243;stico de la enfermedad y las variables cl&#237;nicas asociadas a nefropat&#237;a en pacientes afectados&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal&#46; Se incluyeron pacientes de tres centros de referencia de Argentina&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 72 pacientes &#40;26&#44;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;48<span class="elsevierStyleHsp" style=""></span>a&#241;os&#41;&#58; 30 &#40;41&#44;6&#37;&#41; varones y 42 &#40;58&#44;4&#37;&#41; mujeres&#59; 27 pedi&#225;tricos y 45 adultos&#46; Se detectaron 14 &#171;casos &#237;ndice&#187;&#44; el 50&#37; diagnosticados por nefr&#243;logos&#46; Se hall&#243; nefropat&#237;a en 44 pacientes &#40;61&#37;&#41;&#58; 6 pedi&#225;tricos y 38 adultos&#46; Dos tipos de variables cl&#237;nicas se asociaron a nefropat&#237;a&#58; a&#41;<span class="elsevierStyleHsp" style=""></span>compromiso del sistema nervioso perif&#233;rico &#40;p<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; angioqueratomas &#40;p<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y compromiso auditivo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01-0&#44;001&#41;&#44; siendo estas manifestaciones cl&#237;nicas tempranas del fenotipo m&#225;s severo de la enfermedad&#44; y b&#41;<span class="elsevierStyleHsp" style=""></span>cardiopat&#237;a estructural &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01-0&#44;001&#41; y compromiso del sistema nervioso central &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05-0&#44;01&#41;&#44; que son complicaciones mayores y tard&#237;as&#44; responsables de la morbimortalidad aumentada y la menor expectativa de vida&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusi&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El nefr&#243;logo cumple un rol importante en el diagn&#243;stico de la enfermedad de Fabry&#44; ya que aunque la detecci&#243;n de esta por su compromiso renal significar&#237;a diagn&#243;stico tard&#237;o&#44; debido a que la nefropat&#237;a se asocia a complicaciones tard&#237;as del fenotipo m&#225;s severo de la enfermedad&#46;</p></span>"
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            "titulo" => "Material y m&#233;todos"
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          2 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Background</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The early detection of Fabry nephropathy is of interest to us&#46; Its treatment is more effective in early stages&#46; It has been studied by analysing molecular and tissue biomarkers&#46; These have certain disadvantages that hinder its routine use&#46; The aim of this study is to describe the role of the nephrologist in the diagnosis of the disease&#44; and to describe the clinical variables associated with nephropathy in affected patients&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional study&#46; Patients were included from three reference centres in Argentina&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Seventy two patients were studied &#40;26&#46;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;48<span class="elsevierStyleHsp" style=""></span>years&#41;&#58; 30 of which &#40;41&#46;6&#37;&#41; were men and 42 of which &#40;58&#46;4&#37;&#41; were women&#59; 27 paediatric patients and 45 adults&#46; Fourteen &#8220;index cases&#8221; were detected&#44; 50&#37; of which were diagnosed by nephrologists&#46; Nephropathy was found in 44 patients &#40;61&#37;&#41;&#58; 6 paediatric patients and 38 adults&#46; Two types of clinical variables were associated with nephropathy&#58; &#40;i&#41;<span class="elsevierStyleHsp" style=""></span>peripheral nervous system compromise &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; angiokeratomas &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and auditory compromise &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;01-&#46;001&#41;&#44; with these being early clinical manifestations of the most severe disease phenotype&#44; and &#40;ii&#41;<span class="elsevierStyleHsp" style=""></span>structural heart disease &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01-&#46;001&#41; and central nervous system compromise &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;05-&#46;01&#41;&#44; which are major and late complications&#44; responsible for increased morbidity and mortality and lower life expectancy&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The nephrologist plays an important role in the diagnosis of Fabry nephropathy&#44; although the detection thereof owing to its renal involvement would represent a late diagnosis&#44; because nephropathy is associated with late complications of the most severe disease phenotype&#46;</p></span>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sin nefropat&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">chi<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Var&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3-0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mujer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pedi&#225;trico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adulto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Actividad &#945;-gal-A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62; 0&#44;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disminuida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Compromiso del SNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Compromiso digestivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3-0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&#243;rnea verticilata&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3-0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Angioqueratomas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Compromiso auditivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;01-0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arritmias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62; 0&#44;095&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiopat&#237;a estructural&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;01-0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Compromiso del SNC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;05-0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tabaquismo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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