Share
array:24 [ "pii" => "S2254887418301796" "issn" => "22548874" "doi" => "10.1016/j.rceng.2018.11.003" "estado" => "S300" "fechaPublicacion" => "2019-04-01" "aid" => "1581" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Rev Clin Esp. 2019;219:141-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3 "formatos" => array:2 [ "HTML" => 1 "PDF" => 2 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0014256518302807" "issn" => "00142565" "doi" => "10.1016/j.rce.2018.09.011" "estado" => "S300" "fechaPublicacion" => "2019-04-01" "aid" => "1581" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Rev Clin Esp. 2019;219:141-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 33 "formatos" => array:2 [ "HTML" => 15 "PDF" => 18 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Breve</span>" "titulo" => "Presentación atípica de amiloidosis por transtiretina en un área no endémica" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "141" "paginaFinal" => "144" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Atypical presentation of transthyretin amyloidosis in a non-endemic area" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 568 "Ancho" => 800 "Tamanyo" => 27132 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Familia A. Madre e hijas portadoras de la variante genética Glu74Gln.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Gracia Gutiérrez, E. Bueno Juana, C. Lahuerta Pueyo, S. Menao Guillén, J. Escota Villanueva, M.Á. Aibar Arregui" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Gracia Gutiérrez" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Bueno Juana" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Lahuerta Pueyo" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Menao Guillén" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "Escota Villanueva" ] 5 => array:2 [ "nombre" => "M.Á." "apellidos" => "Aibar Arregui" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887418301796" "doi" => "10.1016/j.rceng.2018.11.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418301796?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256518302807?idApp=WRCEE" "url" => "/00142565/0000021900000003/v1_201903280610/S0014256518302807/v1_201903280610/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2254887419300451" "issn" => "22548874" "doi" => "10.1016/j.rceng.2019.01.011" "estado" => "S300" "fechaPublicacion" => "2019-04-01" "aid" => "1623" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "edi" "cita" => "Rev Clin Esp. 2019;219:145-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Internists and death in the hospital" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "145" "paginaFinal" => "146" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Los internistas y la muerte en el hospital" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. Plaza Canteli, J. Marco Martínez" "autores" => array:2 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Plaza Canteli" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Marco Martínez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256519300207" "doi" => "10.1016/j.rce.2019.01.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256519300207?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887419300451?idApp=WRCEE" "url" => "/22548874/0000021900000003/v1_201903280618/S2254887419300451/v1_201903280618/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2254887419300062" "issn" => "22548874" "doi" => "10.1016/j.rceng.2018.09.007" "estado" => "S300" "fechaPublicacion" => "2019-04-01" "aid" => "1586" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2019;219:130-40" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "First hospital admission due to heart failure: In-hospital mortality and patient profile" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "130" "paginaFinal" => "140" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Primera hospitalización por insuficiencia cardiaca: mortalidad hospitalaria y perfil del paciente" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Masip, F. Formiga, M. Fernández-Castañer, P. Fernández, J. Comín-Colet, X. Corbella" "autores" => array:6 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Masip" ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Formiga" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Fernández-Castañer" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Fernández" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "Comín-Colet" ] 5 => array:2 [ "nombre" => "X." "apellidos" => "Corbella" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256518302893" "doi" => "10.1016/j.rce.2018.09.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256518302893?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887419300062?idApp=WRCEE" "url" => "/22548874/0000021900000003/v1_201903280618/S2254887419300062/v1_201903280618/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief Original</span>" "titulo" => "Atypical presentation of transthyretin amyloidosis in a non-endemic area" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "141" "paginaFinal" => "144" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Gracia Gutiérrez, E. Bueno Juana, C. Lahuerta Pueyo, S. Menao Guillén, J. Escota Villanueva, M.Á. Aibar Arregui" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Gracia Gutiérrez" "email" => array:1 [ 0 => "agraciagut@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Bueno Juana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Lahuerta Pueyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "S." "apellidos" => "Menao Guillén" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "Escota Villanueva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "M.Á." "apellidos" => "Aibar Arregui" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Medicina Interna, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Bioquímica Clínica y Patología Molecular, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Cardiología, Hospital Clínico Universitario Lozano Blesa, ISS-Aragón, Zaragoza, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Presentación atípica de amiloidosis por transtiretina en un área no endémica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 568 "Ancho" => 800 "Tamanyo" => 27132 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Family A. Mother and daughter carriers of the genetic variant Glu74Gln.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic amyloidoses are diseases characterized by the extracellular deposit of amyloid material.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> The most common types of amyloidosis are the primary type or AL, the secondary type or AA and transthyretin amyloidosis (ATTR).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Transthyretin (TTR) is the carrier protein of thyroxine and retinol<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> and has a natural tendency to form amyloid fibrils that are then deposited, causing cell damage and toxicity.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">4,5</span></a> There are 2 types of TTR amyloidosis: a senile variant or wild-type ATTR (wt-ATTR) and another resulting from pathogenic variants of the TTR gene (m-ATTR) of which approximately 100 pathogenic variants have been described.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">1,3,6–8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">M-ATTR is a progressive and fatal disease, with considerable variability in the clinical manifestations, which are predominantly neurological (in the form of sensory-motor neuropathy) and cardiac (in the form of cardiomyopathy). This variability depends on the genetic variant, transmitted in an autosomal dominant manner with variable phenotypic penetrance, and on factors such as the geographical area, leading to significant difficulty in its diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">3,5,7,9,10</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We selected 63 patients with suspected TTR amyloidosis in the University Clinic Hospital of Zaragoza, treated in the internal medicine and cardiology departments between May 1, 2016 and June 30, 2017. The study was authorized by the Clinical Research Ethics Committee of Aragon (CEICA).</p><p id="par0025" class="elsevierStylePara elsevierViewall">Inclusion criteria:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">Heart failure with preserved ejection fraction with no history of valvular heart disease or arterial hypertension.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">History of dysautonomia or bilateral carpel tunnel syndrome (CTS).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Polyneuropathy of unknown etiology.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Imaging tests consistent with amyloidosis: scintigraphy (uptake of 99mTc-DPD in the heart), echocardiogram (thickening of the left ventricular free wall [>12<span class="elsevierStyleHsp" style=""></span>mm] or of the septum [>13<span class="elsevierStyleHsp" style=""></span>mm] and/or granular pattern), cardiac magnetic resonance imaging (MRI) (late gadolinium enhancement).</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Electroneurography/electromyography compatible with familial amyloid polyneuropathy.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">History of amyloidosis of unknown origin.</p></li></ul></p><p id="par0060" class="elsevierStylePara elsevierViewall">Exclusion criteria:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Underage patients.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Patient refusal.</p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">We included patients who met 2 or more criteria to obtain a sample with a high probability of ATTR. Once the patients were selected, they were informed about the study and asked for their appropriate consent. They then underwent a genetic study using Sanger sequencing. First-degree relatives of those patients with positive results were offered the option of a study.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">We studied 63 patients, half of whom were male, with a mean age of 73.08 (±17.8) years, and 95% were Spanish. The symptoms presented at diagnosis were predominantly cardiac (dyspnea, chest pain and edema) and neurological (paresthesia and muscle weakness). There were 7 cases positive for m-ATTR distributed among 3 families and 3 polymorphisms not associated with disease.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The 3 cases with genetic variants of TTR are described below.</p><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Family A</span>. Genetic variant Glu74Gln (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). A 43-year-old woman from Romania, with no family history but with a history of bilateral CTS who was admitted for decompensated heart failure (HF). During her hospitalization, the patient underwent numerous additional tests, which revealed restrictive cardiomyopathy in the echocardiogram and suspected amyloidosis in the cardiac MRI. The genetic study found the genetic variant Glu74Gln. While on the waiting list for a heart and liver transplant, the patient died after experiencing a massive ischemic stroke. Genetic counseling was provided to her 2 children, a healthy male and a daughter who carried the same genetic variant in heterozygosity. The daughter is currently asymptomatic and in follow-up in internal medicine consultations.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Family B.</span> Genetic variant Val142Ile, in heterozygosity (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). An 86-year-old Spanish woman, with no family history but with a history of arterial hypertension (AHT), atrial fibrillation and HF, was admitted for symptoms of decompensated HF. Tests revealed symmetrical ventricular hypertrophy suggestive of senile amyloidosis. The results of a monoclonal gammopathy study were negative, NT-proBNP levels were high, and fine-needle aspiration cytology of abdominal fat was negative. Scintigraphy was not performed. A genetic study was requested, which showed the genetic variant Val142Ile. The patient's 90-year-old sister was also examined. The sister had a history of AHT, HF and macular degeneration and was admitted for syncope secondary to a complete atrioventricular block. The echocardiogram revealed moderate valvular heart disease and preserved ejection fraction. Neither scintigraphy nor biopsy was performed on the sister. The genetic study detected the same variant as in her sister, Val142Ile. The genetic study was performed on the rest of the family, detecting the same genetic variant in a 42-year-old nephew, who was asymptomatic. The results of additional tests on the nephew showed normal values.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Family C.</span> Genetic variant Val142Ile, in homozygosity (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). A 59-year-old Ghanaian woman, with a medical history of AHT, type 2 DM, dyslipidemia, lacunar stroke without sequela, chronic pulmonary thromboembolism and pulmonary fibrosis and user of home oxygen therapy. The echocardiogram revealed infiltrative cardiomyopathy with severe concentric hypertrophy, preserved systolic function, restrictive filling pattern and severe pulmonary hypertension. The cardiac MRI suggested cardiac amyloidosis as the first option. The patient presented dyspnea (New York Heart Association functional class II-III). Myocardial scintigraphy revealed intense uptake in both ventricles. The results of the fine-needle aspiration cytology of subcutaneous fat were negative, and a genetic study was positive for ATTR due to the genetic variant Val142Ile in homozygosity. The patient's daughter underwent the genetic study, which revealed that the daughter carried the same pathogenic variant. Two of the patient's nieces underwent the test with negative results. We assume that the parents of the index case were carriers of the genetic variant due to the involvement in homozygosity of the index case.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">We present the pathogenic variants of 3 families with compatible symptoms and positive genetic study results for amyloidogenic variants. The Zaragoza area (Aragon) is a nonendemic area for m-ATTR. This sample is obviously highly selected, and the results of this study cannot therefore be extrapolated to the general population. The study should also not be viewed as a prevalence study. However, the presence of 3 cases of a rare disease in a sample of only 63 patients has a certain value and suggests we are faced with an underdiagnosed disease.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The first family presented the pathogenic variant Glu74Gln, whose initial involvement is usually CTS, with subsequently cardiac manifestations.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> This genetic variant has been described in 2 Romanian individuals, as well as in our index case.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> These data suggest that there are clusters in regions considered nonendemic, from which we have no data.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The other 2 families presented the pathogenic variant Val142Ile, one in heterozygosity and the other in homozygosity. As described in the literature, this genetic variant is the most common in the US (23%), especially in individuals of African-American descent, and is rare in other ethnic groups.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> The frequency of this variant in the white and Hispanic population in the US is 0.44% and 0%, respectively.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a> In our population, the first family described is Spanish, and the second was Ghanaian, which shows that cases can occur in nonendemic areas, native and imported.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The Val142Ile allele generally presents in heterozygosity and with cardiac symptoms.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">5,6</span></a> Our 2 families started with cardiac impairment and, in the homozygous patient, with pulmonary involvement categorized as “fibrosis”, which we have not been able to confirm due to the negative results of the lung biopsy. Pulmonary involvement in m-ATTR consists mainly of diffuse alveolar septal amyloidosis, which can be confused with pulmonary fibrosis if amyloid deposits are not specifically searched for.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In our series, 2 families presented with the variant Val142Ile, one of the patients in homozygosity and the others in heterozygosity. Although not the rule, homozygous cases typically develop symptoms approximately 10 years before heterozygous cases.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">13,14</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Certain gene variants are characterized by their strong genotype/phenotype correlation and are associated with predominantly neurological (Val50Met), cardiac (Val142Ile) or mixed (Thr80Ala) disease.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">15</span></a> Nevertheless, this disease has a considerable phenotypic variability, which impedes its diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">15,16</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">This difficulty is greater in nonendemic areas and in atypical cases, such as the ones we presented.</p><p id="par0140" class="elsevierStylePara elsevierViewall">The first case is significant due to its rare and imported variant. The second case stands out for being a variant with homozygous involvement and with possible pulmonary involvement. The third case is important for being diagnosed in a native family from a nonendemic area affected by a pathogenic variant almost exclusively of the African-American population.</p><p id="par0145" class="elsevierStylePara elsevierViewall">This study highlights the need to include ATTR in our differential diagnosis of diseases as common as peripheral neuropathy and heart failure with preserved ejection fraction, especially in young patients with no clear etiology.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Our study's limitations include the small sample size, due to the fact that we decided to require 2 inclusion criteria from the patients, which increased the possibility of recruiting positive patients; however, just one of the previously mentioned criteria would have been sufficient to include them in the differential diagnosis of ATTR.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0155" class="elsevierStylePara elsevierViewall">ATTR is a rare disease that manifests mainly in endemic areas but can appear in any population, both in native and immigrant patients. Maintaining a high index of suspicion is essential for initiating the appropriate diagnostic methods for an early diagnosis of the disease.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">The present study was partially funded by <span class="elsevierStyleGrantSponsor" id="gs1">Pfizer</span>.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1171506" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1095905" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1171505" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedente y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1095906" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-20" "fechaAceptado" => "2018-09-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1095905" "palabras" => array:5 [ 0 => "Hereditary amyloidosis" 1 => "Transthyretin" 2 => "Cardiomyopathy" 3 => "Polyneuropathy" 4 => "Heterogeneous disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1095906" "palabras" => array:5 [ 0 => "Amiloidosis hereditaria" 1 => "Transtiretina" 2 => "Miocardiopatía" 3 => "Polineuropatía" 4 => "Enfermedad heterogénea" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There are 2 types of amyloidosis caused by transthyretin deposits: the wild type (wt-ATTR) and the mutant type (m-ATTR), transmitted by autosomal dominant inheritance with variable penetrance, manifesting with neurological and/or cardiac symptoms. We report on 3 families affected by m-ATTR diagnosed in a nonendemic area.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We studied 63 patients with a high suspicion of ATTR. The diagnosis was subsequently performed by magnification through polymerase chain reaction of DNA. For the positive cases, we studied the first-degree relatives.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We detected 7 positive cases of m-ATTR, distributed among 3 families (Glu74Gln, Val142Ile in heterozygosity and Val142Ile in homozygosity), and 3 cases of nonpathogenic variants.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Hereditary ATTR is a rare disease but is present in nonendemic areas and should therefore be considered in the differential diagnosis of patients with polyneuropathy and/or heart failure with preserved ejection fraction.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedente y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Existen 2 tipos de amiloidosis producidas por depósitos de transtiretina, el tipo salvaje (wt-ATTR) y el tipo mutante (m-ATTR), transmitido por herencia autosómica dominante con penetrancia variable, manifestándose con clínica neurológica y/o cardíaca. Describimos 3 familias afectadas por m-ATTR diagnosticadas en un área no endémica.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 63 pacientes con alta sospecha de amiloidosis TTR. Posteriormente, el diagnóstico se realizó por amplificación mediante PCR de ADN y en los casos positivos se estudiaron a los familiares de primer grado.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se detectaron 7 casos positivos para m-ATTR, distribuidos en 3 familias (Glu74Gln, Val142Ile en heterocigosis y Val142Ile en homocigosis) y 3 casos de variantes no patogénicas.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La amiloidosis hereditaria por TTR es una enfermedad rara, pero presente en áreas no endémicas, por lo que debe tenerse en cuenta en el diagnóstico diferencial de los pacientes con polineuropatía y/o insuficiencia cardiaca con fracción de eyección preservada.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedente y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gracia Gutiérrez A, Bueno Juana E, Lahuerta Pueyo C, Menao Guillén S, Escota Villanueva J, Aibar Arregui MÁ. Presentación atípica de amiloidosis por transtiretina en un área no endémica. Rev Clin Esp. 2019;219:141–144.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 568 "Ancho" => 800 "Tamanyo" => 27132 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Family A. Mother and daughter carriers of the genetic variant Glu74Gln.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1087 "Ancho" => 1200 "Tamanyo" => 83333 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Family B. Sisters and nephew carriers of the genetic variant Val142Ile. Family C. Mother with the genetic variant Val142Ile in homozygous form. Daughter carrier of the same genetic variant.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0085" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Wechalekar" 1 => "J. Gilmore" 2 => "P. Hawkins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(15)01274-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2016" "volumen" => "387" "paginaInicial" => "2641" "paginaFinal" => "2654" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26719234" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0090" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification international society of amyloidosis 2016 nomenclature guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Sipe" 1 => "M. Benson" 2 => "J. Buxbaum" 3 => "S. Ikeda" 4 => "G. Merlini" 5 => "M. Saraiva" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/13506129.2016.1257986" "Revista" => array:6 [ "tituloSerie" => "Amyloid" "fecha" => "2016" "volumen" => "23" "paginaInicial" => "209" "paginaFinal" => "213" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27884064" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0095" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac transthyretin amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.N. Dungu" 1 => "L.J. Anderson" 2 => "C.J. Whelan" 3 => "P.N. Hawkins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/heartjnl-2012-301924" "Revista" => array:6 [ "tituloSerie" => "Heart" "fecha" => "2012" "volumen" => "98" "paginaInicial" => "1546" "paginaFinal" => "1554" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22888163" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0100" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis, prognosis and therapy of transthyretin amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Gertz" 1 => "M.D. Benson" 2 => "P.J. Dyck" 3 => "M. Grogan" 4 => "T. Coelho" 5 => "M. Cruz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2015.09.075" "Revista" => array:7 [ "tituloSerie" => "JACC" "fecha" => "2015" "volumen" => "66" "paginaInicial" => "2451" "paginaFinal" => "2466" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26610878" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S2213219818302897" "estado" => "S300" "issn" => "22132198" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0105" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transthyretin amyloidosis: an under-recognized neuropathy and cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Galant" 1 => "P. Westermark" 2 => "J. Higaki" 3 => "Chakrabartty" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1042/CS20160413" "Revista" => array:6 [ "tituloSerie" => "Clin Sci" "fecha" => "2017" "volumen" => "131" "paginaInicial" => "395" "paginaFinal" => "409" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28213611" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0110" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transthyretin cardiac amyloidosis: pathogenesis, treatments, and emerging role in heart failure with preserved ejection fraction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V.K. Ton" 1 => "M. Mukherjee" 2 => "D.P. Judge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4137/CMC.S15719" "Revista" => array:6 [ "tituloSerie" => "Clin Med Insights Cardiol" "fecha" => "2015" "volumen" => "8" "paginaInicial" => "39" "paginaFinal" => "44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25628512" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0115" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O. Suhr" 1 => "E. Lundgren" 2 => "P. Westermark" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/joim.12585" "Revista" => array:7 [ "tituloSerie" => "J Intern Med" "fecha" => "2017" "volumen" => "281" "paginaInicial" => "337" "paginaFinal" => "347" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28093848" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0091674909027341" "estado" => "S300" "issn" => "00916749" ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0120" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prevalence and management of systemic amyloidosis in western countries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Nienhuis" 1 => "J. Bijzet" 2 => "B. Hazenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Kidney Dis" "fecha" => "2016" "volumen" => "2" "paginaInicial" => "1" "paginaFinal" => "9" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0125" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guideline of transthyretin-related hereditary amyloidosis for clinicians" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Ando" 1 => "T. Coelho" 2 => "J. Berk" 3 => "M. Waddington" 4 => "B. Ericzon" 5 => "S. Ikeda" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Rare Dis" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "31" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0130" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current concepts of cardiac amyloidosis. Diagnosis, clinical management, and the need for collaboration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Ritts" 1 => "R. Cornell" 2 => "K. Swiger" 3 => "J. Singh" 4 => "S. Goodman" 5 => "D.J. Lenihan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Heart Failure Clin" "fecha" => "2017" "volumen" => "13" "paginaInicial" => "409" "paginaFinal" => "416" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0135" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Amiloidosis cardíaca secundaria a la mutación familiar Glu54Gln del gen de la transtiretina" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I. Torres-Courchoud" 1 => "R. Martínez-Gil" 2 => "M.A. Aibar-Arregui" 3 => "A. Andrés-Gracia" 4 => "M.A. Torralba-Cabeza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rec.2016.07.001" "Revista" => array:6 [ "tituloSerie" => "Rev Esp Cardiol" "fecha" => "2017" "volumen" => "70" "paginaInicial" => "297" "paginaFinal" => "299" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27519456" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0140" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Amyloidosis of the lung" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Khoor" 1 => "T. Colby" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5858/arpa.2016-0102-RA" "Revista" => array:6 [ "tituloSerie" => "Arch Pathol Lab Med" "fecha" => "2017" "volumen" => "141" "paginaInicial" => "247" "paginaFinal" => "254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28134587" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0145" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.N. Buxbaum" 1 => "F.L. Ruberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/gim.2016.200" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2017" "volumen" => "19" "paginaInicial" => "733" "paginaFinal" => "742" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28102864" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0150" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Homozygosity for the V122I mutation in transthyretin is associated with earlier onset of cardiac amyloidosis in the African American population in the seventh decade of life" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Reddi" 1 => "S. Jenkins" 2 => "J. Theis" 3 => "B. Thomas" 4 => "L.H. Connors" 5 => "F. Van Rhee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jmoldx.2013.08.001" "Revista" => array:6 [ "tituloSerie" => "J Mol Diagn" "fecha" => "2014" "volumen" => "16" "paginaInicial" => "68" "paginaFinal" => "74" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24184229" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0155" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-biopsy diagnosis of cardiac transthyretin amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Gillmore" 1 => "M. Maurer" 2 => "R. Falk" 3 => "G. Merlini" 4 => "T. Damy" 5 => "A. Dispenzieri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.116.021612" "Revista" => array:7 [ "tituloSerie" => "Circulation" "fecha" => "2016" "volumen" => "133" "paginaInicial" => "2404" "paginaFinal" => "2412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27143678" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0007091218303180" "estado" => "S300" "issn" => "00070912" ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0160" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Maurer" 1 => "P. Elliott" 2 => "R. Comenzo" 3 => "M. Semigran" 4 => "C. Rapezzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.116.024438" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2017" "volumen" => "135" "paginaInicial" => "1357" "paginaFinal" => "1377" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28373528" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021900000003/v1_201903280618/S2254887418301796/v1_201903280618/en/main.assets" "Apartado" => array:4 [ "identificador" => "1903" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Brief Original" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021900000003/v1_201903280618/S2254887418301796/v1_201903280618/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887418301796?idApp=WRCEE" ]
