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Estudio de un caso de hipoalbuminemia severa
A case study of severe hypoalbuminemia
Belén Vila Dorrioa, Patricia Blanco Ariasc, Marta Diaz Ondinaa, Carmen Santos Quintairosb, Juan Luis Hernández Domingueza, José Dobarro Casadod, Gabriel Jaime Sáncheza,
Autor para correspondencia
a Servicio de Análisis Clínicos. Complejo Hospitalario Universitario, Ourense, España
b Servicio de Medicina Interna, Complejo Hospitalario Universitario, Ourense, España
c Fundación Pública Galega de Medicina Xenómica, Sección Neurogenética, Hospital Clínico Universitario, Santiago de Compostela, A Coruña, España
d Medicina Familiar y Comunitaria, Centro de Salud de Atención Primaria, Carballiño, Ourense, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La hipoalbuminemia es una situaci&#243;n cl&#237;nica en la cual existe&#44; una disminuci&#243;n del nivel s&#233;rico de alb&#250;mina por debajo de 3&#44;5<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#46; Algunos autores la clasifican como &#171;severa&#187; cuando es menor de 2&#44;2<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#46; Existen m&#250;ltiples causas que pueden desencadenar un descenso en la concentraci&#243;n de alb&#250;mina plasm&#225;tica&#44; y que se pueden clasificar en cuatro categor&#237;as&#58; disminuci&#243;n de la s&#237;ntesis&#44; aumento del catabolismo&#44; aumento de las p&#233;rdidas y alteraci&#243;n de la distribuci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">La hipoalbuminemia por disminuci&#243;n de la s&#237;ntesis &#40;insuficiencia hep&#225;tica&#44; desnutrici&#243;n&#41; o aumento del catabolismo &#40;procesos inflamatorios&#41; tiende a ocurrir en un per&#237;odo relativamente largo de semanas o meses&#46; Dado que la alb&#250;mina plasm&#225;tica tiene una vida media de 17 a 20 d&#237;as y que solo un 20-30&#37; de los hepatocitos sintetizan alb&#250;mina en un determinado momento&#44; existe una gran capacidad de reserva en estas situaciones<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Las p&#233;rdidas de alb&#250;mina se producen por hemorragias&#44; nefropat&#237;as&#44; enteropat&#237;a perdedora de prote&#237;nas y p&#233;rdidas exudativas &#40;quemaduras&#44; dermatopat&#237;as y drenajes quir&#250;rgicos&#41;&#46; Una disminuci&#243;n significativa de la alb&#250;mina s&#233;rica como consecuencia de estas p&#233;rdidas&#44; puede ocurrir en cuesti&#243;n de horas<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">La alteraci&#243;n en la distribuci&#243;n de la alb&#250;mina entre los compartimentos intravascular y extravascular es probablemente la causa m&#225;s frecuente de la hipoalbuminemia en el paciente cr&#237;tico&#46; Debido al aumento en la permeabilidad capilar puede producirse una salida r&#225;pida de la alb&#250;mina al espacio intersticial&#46; El movimiento promedio de la alb&#250;mina es solo de 16 horas&#44; por lo que los cambios en la distribuci&#243;n de la alb&#250;mina pueden llevar a hipoalbuminemia en pocas horas&#44; como sucede por ejemplo en la sepsis<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">La consecuencia m&#225;s sensible de la hipoalbuminemia es el desarrollo de edemas&#44; debido a la disminuci&#243;n de la presi&#243;n onc&#243;tica del plasma&#59; y si esta es muy importante pueden aparecer tambi&#233;n&#44; ascitis y derrame pleural<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Espor&#225;dicamente aparecen hipoalbuminemias severas&#44; que parad&#243;jicamente cursan con edemas parciales e incluso ausencia de edema&#46; Es el caso de la analbuminemia cong&#233;nita&#44; antes hipoalbuminemia idiop&#225;tica&#46; Bennhold et al&#46; describieron el primer caso en 1954<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Caso cl&#237;nico</span><p id="par0035" class="elsevierStylePara elsevierViewall">Mujer de 53 a&#241;os&#44; sin antecedentes familiares de ataxia&#46; Hija &#250;nica de padres consangu&#237;neos&#46; Ingresa en Medicina Interna en 2007&#44; para estudio de edema intenso en miembros inferiores&#46; Fue diagnosticada de <span class="elsevierStyleItalic">ataxia de Friedreich</span> a los 38 a&#241;os en 1993&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">De la revisi&#243;n de la historia cl&#237;nica y los informes aportados por la paciente&#44; observamos que existe ataxia de inicio temprano &#40;antes de los 8 a&#241;os&#41;&#59; neuropat&#237;a perif&#233;rica de predominio distal con d&#233;ficit motor que condujo a cuadriplejia a los 45 a&#241;os&#59; marcada atrofia cerebelosa&#59; hipoalbuminemia persistente&#59; pies cavos y escoliosis&#46; No presenta retraso mental&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Al ingreso y tras las exploraciones y estudios realizados&#44; se encuentra&#58; edemas en miembros inferiores&#44; con pulsos perif&#233;ricos presentes&#59; movilidad abolida con arreflexia generalizada e hipoestesia en las 4 extremidades&#59; severa dismetr&#237;a bilateral&#59; obesidad y marcada lipodistrofia&#59; no presenta ascitis ni cardiopat&#237;a y se observa <span class="elsevierStyleItalic">nistagmus</span> marcado&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">En cuanto a la enfermedad degenerativa de la paciente&#44; no puede excluirse el diagn&#243;stico previo de ataxia de Friedreich&#44; pero llama la atenci&#243;n la intensa afectaci&#243;n neurop&#225;tica y la atrofia cerebral&#44; por lo que deber&#237;a tomarse en cuenta la posible existencia y&#47;o solapamiento de otras ataxias sensitivo-motoras hereditarias&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">En el estudio de edemas no se encuentran s&#237;ntomas cl&#237;nicos ni resultados de laboratorio coherentes con p&#233;rdida de prote&#237;nas&#44; malnutrici&#243;n&#44; malabsorci&#243;n&#44; enfermedad autoinmune&#44; parasitosis&#44; ascitis&#44; neoplasia&#44; proceso inflamatorio agudo&#44; etc&#46; Desde el punto de vista bioqu&#237;mico&#44; el hallazgo m&#225;s relevante es la hipoalbuminemia severa &#40;&#60;1<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41;&#44; presente desde hace a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#41;&#46; Los estudios de imagen e histopatol&#243;gicos no revelan nada anormal&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Hip&#243;tesis diagn&#243;stica</span><p id="par0060" class="elsevierStylePara elsevierViewall">Al no poder establecerse el origen de la hipoalbuminemia&#44; se realiza una revisi&#243;n bibliogr&#225;fica exhaustiva para hipoalbuminemia severa&#47;ataxia y se encuentran 2 posibles causas&#58; <span class="elsevierStyleItalic">Analbuminemia</span> y <span class="elsevierStyleItalic">Ataxia de inicio temprano con apraxia ocular e hipoalbuminemia severa</span> &#40;EAOH&#47;AOA&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">La analbuminemia &#91;OMIM&#35;103600&#93;&#44; es un trastorno autos&#243;mico recesivo&#44; en que los individuos afectados &#40;homocigotos&#41; presentan una virtual ausencia de alb&#250;mina circulante&#44; pero parad&#243;jicamente cursa con edemas parciales e incluso ausencia de edema<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a><span class="elsevierStyleItalic">&#46;</span></p><p id="par0070" class="elsevierStylePara elsevierViewall">EAOH&#47;AOA forma parte del grupo de ataxias cerebelosas autos&#243;micas recesivas &#40;ARCA&#41;&#44; un conjunto heterog&#233;neo de enfermedades que incluyen la ataxia de Friedreich&#44; la de mayor frecuencia relativa &#40;38&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">AOA se presenta como 2 entidades diferentes&#58; ataxia con apraxia ocular tipo 1 &#40;AOA1&#41; y tipo 2 &#40;AOA2&#41;&#46; Los dos tipos son muy similares&#44; pero est&#225;n causadas por mutaciones en diferentes genes<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">AOA1 &#91;OMIM&#35;208920&#93; fue descrita inicialmente en familias japonesas en 1971&#46; Un fenotipo similar fue descrito en familias portuguesas en 2001&#44; lo que permiti&#243; obtener el mapa de AOA1 en el cromosoma 9p13&#44; seguido de la identificaci&#243;n de las mutaciones en el gen APTX<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;16</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">El gen <span class="elsevierStyleItalic">APTX</span> codifica aprataxina&#44; una prote&#237;na&#44; cuya funci&#243;n a&#250;n se desconoce&#44; pero que podr&#237;a tener un papel importante en los mecanismos de reparaci&#243;n del ADN&#46; Consta de 7 exones&#44; y hasta la fecha&#44; se han encontrado 16 mutaciones diferentes&#46; Todas las mutaciones identificadas hasta ahora se localizan en los exones 5&#44; 6 y 7<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;20</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">AOA1 se sospecha en individuos con ataxia cerebelosa de inicio temprano&#44; apraxia oculomotora&#44; neuropat&#237;a perif&#233;rica e hipoalbuminemia severa&#59; todo ello presente en el fenotipo de la paciente&#44; por lo que se propone estudio molecular del gen APTX&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Por otra parte&#44; se cuestiona el diagn&#243;stico de ataxia de Friedreich ya que la paciente no muestra miocardiopat&#237;a&#44; pero s&#237; atrofia cerebral severa e hipoalbuminemia<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#8211;24</span></a>&#46; El diagn&#243;stico diferencial incluye asimismo&#58; analbuminemia<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#44; AOA2<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#8211;28</span></a>&#44; ataxia con deficiencia de PTT-vitamina E<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;31</span></a>&#59; ataxia tipo SCA2&#44; la cual est&#225; asociada a ataxia cerebelosa y movimientos oculares lentos<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#8211;34</span></a>&#59; enfermedad de Charcot-Marie-Tooth 1 con neuropat&#237;a sensitivo-motora y pies cavos<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#44;36</span></a>&#46; Se realizan estudios moleculares espec&#237;ficos con resultados normales&#46; Las diferencias entre AOA1&#44; AOA2 y ataxia de Friedreich se especifican en la <a class="elsevierStyleCrossRef" href="#tbl2">tabla 2</a>&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p id="par0100" class="elsevierStylePara elsevierViewall">Se extrajo el ADN gen&#243;mico mediante procedimiento automatizado &#40;Chemagic Magnetic Separador Module1&#41;&#44; CHEMAGEN<span class="elsevierStyleSup">&#174;</span><a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a><span class="elsevierStyleItalic">&#46;</span> El protocolo consiste en la separaci&#243;n de &#225;cidos nucleicos con bolas magn&#233;ticas a partir de sangre perif&#233;rica recogida sobre EDTA como anticoagulante&#44; previo consentimiento informado por parte de la paciente&#46; Se amplificaron mediante reacci&#243;n en cadena de la polimerasa &#40;PCR&#41; los 7 exones codificantes y las uniones ex&#243;n-intr&#243;n del transcrito con el marco de lectura m&#225;s largo del gen <span class="elsevierStyleItalic">APTX</span> &#40;n&#250;mero de acceso GenBank NM&#95;175073&#41;&#46; Este an&#225;lisis detecta la pr&#225;ctica totalidad de mutaciones conocidas para <span class="elsevierStyleItalic">APTX</span>&#46; Las condiciones de amplificaci&#243;n consistieron en una desnaturalizaci&#243;n inicial de 3 minutos a 95<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 35 ciclos de 20 segundos a 95<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 30 segundos a 60<span class="elsevierStyleHsp" style=""></span>&#176;C y 40 segundos a 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; con una extensi&#243;n final de 3 minutos a 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; En cada reacci&#243;n se a&#241;adieron 0&#44;75U de GoTaq<span class="elsevierStyleSup">&#174;</span> DNA Polymerase &#40;Promega&#41;&#44; GoTaq<span class="elsevierStyleSup">&#174;</span> DNA Polymerase buffer 1X&#44; magnesio a 1&#44;5<span class="elsevierStyleHsp" style=""></span>mM&#44; cada cebador a 0&#44;2<span class="elsevierStyleHsp" style=""></span>&#956;M y 50<span class="elsevierStyleHsp" style=""></span>ng de ADN gen&#243;mico&#44; en un volumen final total de 25 microlitros&#46; Los productos de PCR se purificaron enzim&#225;ticamente mediante incubaci&#243;n con ExoSAP-IT<span class="elsevierStyleSup">&#174;</span> &#40;USB Corporation&#41; 15 minutos a 37<span class="elsevierStyleHsp" style=""></span>&#176;C e inactivaci&#243;n 15 minutos a 80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">La secuenciaci&#243;n c&#237;clica bidireccional se realiz&#243; con el kit Big Dye<span class="elsevierStyleSup">&#174;</span> Terminator v3&#46;1 &#40;Applied Biosystems&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#44; seguida de la purificaci&#243;n de los productos con Montage SEQ<span class="elsevierStyleInf">96</span> Sequencing Reaction Cleanup kit &#40;Millipore Corporation&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#44; y electroforesis capilar con el secuenciador autom&#225;tico 3730XL DNA Analyzer &#40;Applied Biosystems&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Los cebadores utilizados se recogen en la <a class="elsevierStyleCrossRef" href="#tbl3">tabla 3</a>&#46; Cada ex&#243;n se amplific&#243; por PCR con la pareja de cebadores F y R correspondiente &#40;por ejemplo&#44; ex&#243;n 1&#58; con los cebadores APTX-1F y APTX-1R&#41;&#44; posteriormente el producto de PCR se secuenci&#243; en el sentido directo con dicho cebador F &#40;forward&#41; y sentido inverso con el cebador R &#40;reverse&#41; correspondiente&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Los electroferogramas se analizaron mediante el paquete inform&#225;tico &#171;Staden Package&#187;&#44; dise&#241;ado para el ensamblaje&#44; edici&#243;n y an&#225;lisis de secuencias de ADN<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><p id="par0120" class="elsevierStylePara elsevierViewall">La paciente es portadora de un cambio en homocigosis de una citosina por una timina en el quinto ex&#243;n del gen <span class="elsevierStyleItalic">APTX</span> &#40;NM&#95;175073&#46;1&#58; c&#46;739C<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T&#41;&#44; lo que predice la sustituci&#243;n de un cod&#243;n codificante para el amino&#225;cido arginina por un cod&#243;n de parada&#44; produci&#233;ndose por tanto una prote&#237;na truncada &#40;NP&#95;778243&#46;1&#58; p&#46;R247X&#41;&#46; Esta mutaci&#243;n ha sido descrita previamente como causante de AOA1 por Mosesso et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#44; se presentan los electroferogramas correspondientes al quinto ex&#243;n&#46; Se incluye la secuenciaci&#243;n en ambas direcciones del caso a estudio frente a un caso control&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discusi&#243;n</span><p id="par0130" class="elsevierStylePara elsevierViewall">La hipoalbuminemia es una situaci&#243;n cl&#237;nica muy frecuente<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46; La presencia de edema&#44; hace que en la mayor&#237;a de los casos la causa de la hipoalbuminemia pueda ser explicada<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;5</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Cuando existe hipoalbuminemia marcada sin edema o edema parcial el diagn&#243;stico debe dirigirse hacia analbuminemia cong&#233;nita o EAOH&#47;AOA&#46; La analbuminemia puede ser f&#225;cilmente detectada por los an&#225;lisis de rutina de laboratorio&#44; como electroforesis del suero<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#8211;44</span></a>&#46; En cuanto a EAOH&#47;AOA&#44; entidad diagn&#243;stica relativamente reciente&#44; el estudio es m&#225;s complejo&#44; pues s&#237;ntomas principales como la ataxia y neuropat&#237;a requieren diagn&#243;stico diferencial con otras enfermedades y&#44; la apraxia oculomotora puede aparecer tard&#237;amente o pasar inadvertida en ex&#225;menes rutinarios o estar solapada con la presencia de nistagmus<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;45</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">En el caso que acabamos de exponer&#44; existi&#243; hipoalbuminemia severa durante a&#241;os&#44; casi siempre sin edemas&#59; pero nunca se investig&#243; su origen por distintas razones&#58; bien porque la situaci&#243;n de hipoalbuminemia sin edemas no es habitual en el contexto cl&#237;nico&#59; bien porque se considerara normal en la situaci&#243;n de la paciente &#40;inmovilizaci&#243;n prolongada&#44; obesidad y lipodistrofia&#41; e incluso porque se pensase en un error de laboratorio&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Es probable que la presencia de s&#237;ntomas cl&#237;nicos moderados en relaci&#243;n con la hipoalbuminemia&#44; atribuidos a un efecto compensatorio por el incremento de la s&#237;ntesis de otras prote&#237;nas&#44; que estabilizan la presi&#243;n onc&#243;tica&#59; hizo que no se tomara en cuenta el descenso de alb&#250;mina&#46; En este escenario las alteraciones en el metabolismo de los l&#237;pidos son muy importantes y consisten en un aumento significativo del colesterol total<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46&#44;47</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Los resultados de laboratorio siempre aportan valor a&#241;adido al estudio cl&#237;nico y forman parte importante del proceso diagn&#243;stico&#44; por lo que los informes reiterados por nuestro laboratorio de albumina<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>g&#47;dL debieron ser atendidos&#46; La interpretaci&#243;n de la hipoalbuminemia fue sesgada&#44; pues no se tuvo en cuenta cuando no existi&#243; edema&#46; Sin embargo&#44; cuando se llev&#243; a cabo el estudio a fondo sobre el origen de la misma se pudo descartar el diagn&#243;stico inicial de ataxia de Friedreich y obtener el diagn&#243;stico definitivo de AOA1&#44; si bien es cierto que todav&#237;a no se conoce&#44; a d&#237;a de hoy la causa por la que se produce un descenso tan significativo de alb&#250;mina en AOA1&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">La conclusi&#243;n es que puede presentarse la situaci&#243;n cl&#237;nica de hipoalbuminemia no explicada por los mecanismos habituales&#59; y que independientemente de la presencia de edema o de su baja incidencia&#44; deber&#237;a investigarse siempre su origen&#46;</p></span></span>"
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        4 => array:2 [
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          "titulo" => "Introducci&#243;n"
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        5 => array:2 [
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          "titulo" => "Caso cl&#237;nico"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Hip&#243;tesis diagn&#243;stica"
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        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Material y m&#233;todos"
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        8 => array:2 [
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          "titulo" => "Resultados"
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        9 => array:2 [
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          "titulo" => "Discusi&#243;n"
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        10 => array:2 [
          "identificador" => "xack37229"
          "titulo" => "Agradecimientos"
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        11 => array:1 [
          "titulo" => "Bibliograf&#237;a"
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    "fechaRecibido" => "2011-05-16"
    "fechaAceptado" => "2012-01-17"
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          "palabras" => array:4 [
            0 => "Hipoalbuminemia"
            1 => "Analbuminemia"
            2 => "Ataxia"
            3 => "Apraxia"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Hypoalbuminemia"
            1 => "Analbuminemia"
            2 => "Ataxia"
            3 => "Apraxia"
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    "resumen" => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La ataxia con apraxia oculomotora e hipoalbuminemia severa &#40;AOA&#47;EAOH&#41; es una entidad rara que se caracteriza por un inicio temprano de ataxia cerebelosa de progreso lento&#44; seguida por apraxia oculomotora y neuropat&#237;a perif&#233;rica severa que lleva a la cuadriplejia&#46; Pertenece al grupo de ataxias auts&#243;mocas recesivas &#40;ARCA&#41;&#44; siendo la de mayor frecuencia tras la ataxia de Friedreich&#44; y la primera en poblaci&#243;n japonesa&#46; El diagn&#243;stico definitivo es mediante el estudio molecular del gen APTX que codifica para la aprataxina&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se presenta el caso de una mujer de 52 a&#241;os&#44; con s&#237;ntomas y datos sugerentes desde la infancia que ha sido diagnosticada 30 a&#241;os despu&#233;s&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Ataxia with oculomotor apraxia and severe hypoalbuminemia &#40;AOA&#47;EAOH&#41; is a rare entity characterized by early onset of slowly progressive cerebellar ataxia&#44; followed by oculomotor apraxia and peripheral neuropathy leading to severe quadriplegia&#46; AOA&#47;EAOH belongs to the group of autosomal recessive ataxias&#44; being the most frequent after Friedreich&#39;s ataxia&#46; Definitive diagnosis provided by identification of mutations in the APTX gene encoding aprataxin&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This case study of a 52 year-old woman with childhood onset of the disease&#44; suggested by symptoms and several additional findings&#44; who has been diagnosed 30 years later&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Complemento&#44; C3</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">248&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">70 - 176&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#945;1-antitripsina s&#233;rica</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">210&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">79 - 200&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#945;1-antitripsina fecal</span>&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
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                  \t\t\t\t">&#60; 0&#44;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">mg&#47;g&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">hasta 0&#44;30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Bioqu&#237;mica</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Prote&#237;na</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">g&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">6&#44;0 - 8&#44;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Alb&#250;mina</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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
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                  \t\t\t\t">&#60; 1&#44;0&nbsp;\t\t\t\t\t\t\n
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                  \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">g&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">3&#44;5 - 4&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#945;1-globulinas<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">g&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;1 - 0&#44;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#945;2-globulinas<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">g&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;6 - 1&#44;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#946;-globulinas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#44;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">g&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;6 - 1&#44;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#947;-globulinas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">g&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;7 - 1&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Transferrina</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">394&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">192 - 360&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Creatininio</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;5 - 1&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Colesterol total</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">305&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 200&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Vitamina E</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">11&#44;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL&nbsp;\t\t\t\t\t\t\n
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                  \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&#44;0 - 20&#44;0&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Creatina-cinasa</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">75&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">U&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \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 - 180&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Alanina-aminotransferasa</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
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                  \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">U&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \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 - 45&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Fosfatasa alcalina</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">323&nbsp;\t\t\t\t\t\t\n
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                  \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">U&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \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">75 - 350&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#947;-Glutamiltransferasa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \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">U&#47;L&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
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                  \t\t\t\t">5 - 50&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#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">ng&#47;mL&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&#46;9 - 8&#46;0&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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \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">Negativo&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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Negativo&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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negativo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">mg&#47;dL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \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">Negativo&nbsp;\t\t\t\t\t\t\n
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                  \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">-&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
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                  \t\t\t\t">&#60; 1&#47;40&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Acs&#46; citoplasma neutr&#243;filo</span>&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
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                  \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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 1&#47;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;1&nbsp;\t\t\t\t\t\t\n
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                  \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">UA&nbsp;\t\t\t\t\t\t\n
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                  \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">0-5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Acs&#46; antimieloperoxidasa</span>&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;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0-5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Acs&#46; antitransglutaminasa</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;7&nbsp;\t\t\t\t\t\t\n
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                  \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">U&#47;mL&nbsp;\t\t\t\t\t\t\n
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                  \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">0-10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">AOA1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">AOA2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9q33-34&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9q13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">FXN&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 - 18 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 - 22 a&#241;os&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 - 25 a&#241;os&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atrofia cerebelosa&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;&#44; severa&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;&#44; severa&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 siempre&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiomiopat&#237;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">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">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">S&#237;&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neuropat&#237;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">Sensitivo motora&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">Sensitivo motora&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">Axonal sensitiva&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Corea&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;&#44; desaparece&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;&#44; persiste&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></tr><tr title="table-row"><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">Mioclon&#237;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">S&#237;&#44; desaparece&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;&#44; persiste&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></tr><tr title="table-row"><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">Apraxia oculomotora&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">Temprana y grave&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">Leve a moderada&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></tr><tr title="table-row"><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">Retraso mental&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">A veces&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">A veces&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></tr><tr title="table-row"><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">Hipoalbuminemia&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">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">No&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hipercolesterolemia&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">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">No&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes mellitus&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">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">S&#237;&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#945;-Fetoprote&#237;na&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">Elevada&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></tr><tr title="table-row"><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">Creatinacinasa&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">Elevada&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></tr></tbody></table>
                  """
              ]
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                0 => "xTab204430.png"
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        "descripcion" => array:1 [
          "es" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas diferenciales entre&#58; AOA &#40;AOA1&#47;AOA2&#41; vs ataxia Friedreich</p>"
        ]
      ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los exones codificantes amplificados han sido numerados de forma consecutiva del 1 al 7&#46; La correspondencia con la denominaci&#243;n ex&#243;nica de la secuencia referencia de GenBank NM&#95;175073 es la siguiente&#58; ex&#243;n 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 3&#44; ex&#243;n 2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 4a&#44; ex&#243;n 3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 5b&#44; ex&#243;n 4<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 6&#44; ex&#243;n 5<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 7&#44; ex&#243;n 6<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 8&#44; ex&#243;n 7<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>ex&#243;n 9&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">CEBADORES&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">SECUENCIA &#40;5&#8242;-<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3&#8242;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">APTX-1F&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">acttgcctcaagatgaacagc&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-1R&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">ccctggtgttggctaaaaga&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-2F&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">caataacaggtgattgctaataggc&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-2R&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">ccaagcaccttgccttatgt&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-3F&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">acataaggcaaggtgcttgg&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-3R&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">gattttcacgccacaaacaa&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-4F&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">aaggcaatggagtgaagcag&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-4R&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">tgccaatgtgaaaagcctct&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-5F&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">tcctctctcaaaactgggcta&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-5R&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">aggcagaagtgggaactcaa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-6F&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">gcagaggcttttcccatttt&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="left" valign="\n
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                  \t\t\t\t">APTX-6R&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">tagctttctaggtcccccaag&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTX-7F&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">atacctggcctggcatactg&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
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                  \t\t\t\t">APTX-7R&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">ctctacattgtggccactcaa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Cebadores utilizados para la amplificaci&#243;n por PCR y para la secuenciaci&#243;n c&#237;clica bidireccional de los siete exones codificantes del gen APTX</p>"
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        "texto" => "<p id="par0160" class="elsevierStylePara elsevierViewall">Agradecemos al profesor Lorenzo Minchiotti &#40;<span class="elsevierStyleItalic">Department of Biochemistry &#171;A&#46; Castellani&#187; University of Pav&#237;a&#46; Italy</span>&#41; la ayuda que nos ha prestado en el estudio de este caso y la realizaci&#243;n del estudio molecular del gen ALB&#46;</p>"
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ISSN: 18884008
Idioma original: Español
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