Clinical report
Hb Burgos (α1 CD64(E13)(Asp→Asn)): A new hemoglobin variant detected during follow-up of diabetic patients
Hb Burgos (α1 CD64(E13)(Asp→Asn)): una nueva variante de hemoglobina detectada durante la monitorización de pacientes con diabetes
Read
105
Timeswas read the article
28
Total PDF
77
Total HTML
Share statistics
array:24 [ "pii" => "S2387020615000078" "issn" => "23870206" "doi" => "10.1016/j.medcle.2014.07.001" "estado" => "S300" "fechaPublicacion" => "2015-01-06" "aid" => "3120" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2014" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2015;144:26-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 105 "formatos" => array:2 [ "HTML" => 77 "PDF" => 28 ] ] "Traduccion" => array:1 [ "es" => array:18 [ "pii" => "S0025775314006940" "issn" => "00257753" "doi" => "10.1016/j.medcli.2014.07.035" "estado" => "S300" "fechaPublicacion" => "2015-01-06" "aid" => "3120" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "subdocumento" => "crp" "cita" => "Med Clin. 2015;144:26-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 240 "formatos" => array:2 [ "HTML" => 146 "PDF" => 94 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Nota clínica</span>" "titulo" => "Hb Burgos (α<span class="elsevierStyleInf">1</span> CD64(E13)(Asp→Asn)): una nueva variante de hemoglobina detectada durante la monitorización de pacientes con diabetes" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "26" "paginaFinal" => "29" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Hb Burgos (α<span class="elsevierStyleInf">1</span> CD64(E13)(Asp→Asn)): A new hemoglobin variant detected during follow-up of diabetic patients" ] ] "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" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2341 "Ancho" => 3250 "Tamanyo" => 302436 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A) Secuenciación directa: Hb Burgos (α<span class="elsevierStyleInf">1</span> 64(E13) Asp→Asn): GAC→AAC en estado heterocigoto. B) Secuenciación directa: Hb Burgos (α<span class="elsevierStyleInf">1</span> 64(E13) Asp→Asn): GAC→AAC en estado homocigoto.</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Hb: hemoglobina</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Félix de la Fuente-Gonzalo, Jorge Martínez Nieto, María José Torrejón, Luis Antonio Mayor, Diego Velasco, Fernando Ataulfo González Fernández, Paloma Ropero Gradilla" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Félix" "apellidos" => "de la Fuente-Gonzalo" ] 1 => array:2 [ "nombre" => "Jorge" "apellidos" => "Martínez Nieto" ] 2 => array:2 [ "nombre" => "María José" "apellidos" => "Torrejón" ] 3 => array:2 [ "nombre" => "Luis Antonio" "apellidos" => "Mayor" ] 4 => array:2 [ "nombre" => "Diego" "apellidos" => "Velasco" ] 5 => array:2 [ "nombre" => "Fernando Ataulfo" "apellidos" => "González Fernández" ] 6 => array:2 [ "nombre" => "Paloma" "apellidos" => "Ropero Gradilla" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020615000078" "doi" => "10.1016/j.medcle.2014.07.001" "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/S2387020615000078?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775314006940?idApp=UINPBA00004N" "url" => "/00257753/0000014400000001/v1_201412160101/S0025775314006940/v1_201412160101/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020615000066" "issn" => "23870206" "doi" => "10.1016/j.medcle.2013.12.001" "estado" => "S300" "fechaPublicacion" => "2015-01-06" "aid" => "2864" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2015;144:30-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 253 "formatos" => array:2 [ "HTML" => 116 "PDF" => 137 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "The motor organization of cerebral cortex and the role of the mirror neuron system. Clinical impact for rehabilitation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "30" "paginaFinal" => "34" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Organización motora del córtex cerebral y el papel del sistema de las neuronas espejo. Repercusiones clínicas para la rehabilitación" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Laia Sallés, Xavier Gironès, José Vicente Lafuente" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Laia" "apellidos" => "Sallés" ] 1 => array:2 [ "nombre" => "Xavier" "apellidos" => "Gironès" ] 2 => array:2 [ "nombre" => "José Vicente" "apellidos" => "Lafuente" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775314000700" "doi" => "10.1016/j.medcli.2013.12.013" "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/S0025775314000700?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020615000066?idApp=UINPBA00004N" "url" => "/23870206/0000014400000001/v1_201509042040/S2387020615000066/v1_201509042040/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S238702061500008X" "issn" => "23870206" "doi" => "10.1016/j.medcle.2014.07.002" "estado" => "S300" "fechaPublicacion" => "2015-01-06" "aid" => "3082" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2015;144:24-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 187 "formatos" => array:2 [ "HTML" => 116 "PDF" => 71 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "New perspectives for the treatment of alcoholism" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "24" "paginaFinal" => "25" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nuevas perspectivas para el tratamiento del alcoholismo" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Antoni Gual, Laia Miquel" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Antoni" "apellidos" => "Gual" ] 1 => array:2 [ "nombre" => "Laia" "apellidos" => "Miquel" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S002577531400579X" "doi" => "10.1016/j.medcli.2014.07.020" "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/S002577531400579X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061500008X?idApp=UINPBA00004N" "url" => "/23870206/0000014400000001/v1_201509042040/S238702061500008X/v1_201509042040/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Clinical report</span>" "titulo" => "Hb Burgos (α<span class="elsevierStyleInf">1</span> CD64(E13)(Asp→Asn)): A new hemoglobin variant detected during follow-up of diabetic patients" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "26" "paginaFinal" => "29" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Félix de la Fuente-Gonzalo, Jorge Martínez Nieto, María José Torrejón, Luis Antonio Mayor, Diego Velasco, Fernando Ataulfo González Fernández, Paloma Ropero Gradilla" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Félix" "apellidos" => "de la Fuente-Gonzalo" "email" => array:1 [ 0 => "felixfuenteg@hotmail.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" => "Jorge" "apellidos" => "Martínez Nieto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "María José" "apellidos" => "Torrejón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Luis Antonio" "apellidos" => "Mayor" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Diego" "apellidos" => "Velasco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Fernando Ataulfo" "apellidos" => "González Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Paloma" "apellidos" => "Ropero Gradilla" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Hospital Clínico San Carlos, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Reina Sofía, Tudela, Navarra, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Laboratorio BR Salud, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hb Burgos (α<span class="elsevierStyleInf">1</span> CD64(E13)(Asp→Asn)): una nueva variante de hemoglobina detectada durante la monitorización de pacientes con diabetes" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2331 "Ancho" => 3251 "Tamanyo" => 368625 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">(A) Direct sequencing: Hb Burgos (α<span class="elsevierStyleInf">1</span> 64 (E13) Asp→Asn):GAC→AAC in heterozygous state. (B) Direct sequencing: Hb Burgos (α<span class="elsevierStyleInf">1</span> 64(E13) Asp→Asn):GAC→AAC in homozygote state. Hb: haemoglobin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Since the last century, the <span class="elsevierStyleItalic">gold standard</span> technique for haemoglobin (Hb) detection and quantification is ion-exchange <span class="elsevierStyleItalic">high performance liquid chromatography</span> (HPLC). This technique is also used to control <span class="elsevierStyleItalic">diabetes mellitus</span> by measuring the glycosylated haemoglobin (HbA<span class="elsevierStyleInf">1c</span>).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> This last function makes it possible to identify asymptomatic variants that could not be revealed otherwise.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In some cases these variants may cause analytical interference in HbA<span class="elsevierStyleInf">1</span> measurement, risking appropriate diagnosis and treatment for diabetes.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this study we have characterised a new variant of Hb that was diagnosed in 4 patients at the time they underwent an HbA<span class="elsevierStyleInf">1</span> control test.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">The patients, all of them Caucasian males native to Navarra, Madrid, and Burgos, were referred to us because they presented an anomalous peak during the HbA<span class="elsevierStyleInf">1c</span> control, which was done by means of ion-exchange HPLC (Tosoh G8; Tosoh Bioscience, Tokyo, Japan).</p><p id="par0025" class="elsevierStylePara elsevierViewall">The HbA<span class="elsevierStyleInf">2</span> and HbF quantification, as well as the Hb analysis were done by means of ion-exchange HPLC following the short-term program for the Variant™ II of Bio-Rad (BioRad Variant™ II β-thalassemia Short Program; Bio-Rad, Hercules, CA, U.S.). Furthermore, the samples were analysed by zonal capillary electrophoresis using the Sebia system (Sebia Capillarys Flex) and the reactive agents from the <span class="elsevierStyleItalic">kit</span> provided by the business (Capillarys Haemoglobin [E] kit; Sebia, Norcross, GA, U.S.). The globin chains were separated by reversed phase HPLC, as previously published.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Haematological data was obtained by means of an Automatic haematology analyser (Coulter<span class="elsevierStyleSup">®</span> LH750 Analyzer; Beckman Coulter, Brea, CA, U.S.).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The molecular study required the automatic extraction of genomic DNA (BioRobot<span class="elsevierStyleSup">®</span> EZ1™; Qiagen GmbH, Hilden, Germany) and its subsequent quantification with NanoDrop<span class="elsevierStyleSup">®</span> 1000 (Thermo Scientific, Wilmington, DE, U.S.).</p><p id="par0040" class="elsevierStylePara elsevierViewall">The most frequent mutations causing alternations in α genes were analysed with α-globin StripAssay<span class="elsevierStyleSup">®</span> (ViennaLab Diagnostic GmbH, Vienna, Austria). The molecular characterization required selective amplification of genes α and their subsequent automatic sequencing in an ABI PRISM sequencer<span class="elsevierStyleSup">®</span> 3100 Genetic Analyzer (Applied Biosystems, Foster City, CA, U.S.) and with the commercial kit ABI PRISM<span class="elsevierStyleSup">®</span> BigDye<span class="elsevierStyleSup">®</span> Terminator v1.1 Cycle Sequencing Ready Reaction Kit (PE Applied BioSystems, Foster City, CA, U.S.).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">A new clinically silent Hb structural variant was detected, by means of ion-exchange HPLC, during HbA<span class="elsevierStyleInf">1c</span> measurement, at a retention time (RT) of 1.02<span class="elsevierStyleHsp" style=""></span>min, altering the normal pattern (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The Hb analysis by means of ion-exchange HPLC revealed the existence of a peak in the HbS window, involving between 13 and 34.3%; there was, as well, a 4.68<span class="elsevierStyleHsp" style=""></span>min RT adjacent peak. This reaction was confirmed by means of zonal capillary electrophoresis, with anomalous peaks in areas Z6 and Z1, respectively. In the globin chains study by reversed phase HPLC, only the β and α globin chains were separated (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><p id="par0055" class="elsevierStylePara elsevierViewall">The selective sequencing of gene <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span> showed the mutation <span class="elsevierStyleUnderline">G</span>AC><span class="elsevierStyleUnderline">A</span>AC in codon 64 from exon 2 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), substituting aspartic acid amino acid (Asp) for asparagine (Asn). Said variant was called Hb Burgos (α<span class="elsevierStyleInf">1</span>64(E13)Asp>Asn; HBA1:c.193G>A), because the first patient was a native of that province. This mutation was identified at the stage of heterozygosis in 3 patients, whereas in the fourth patient, it was diagnosed at the homozygote stage (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Both the haematological parameters and the genotype of study subjects are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The HbA<span class="elsevierStyleInf">2</span> values oscillated between 1.1 and 2.2%.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">In the Hb Burgos variant, the affected residue is the 64th in the globin chain α<span class="elsevierStyleInf">1</span>, located on the external surface of the molecule (helix E13), which makes it easier to separate by means of electrophoretic and chromatographic techniques, since the replacement of Asp amino acid for Asn amino acid turns the molecule more cathodic than the HbA. This change does not imply any functional alternation to Hb, thus, from a clinical standpoint, it is asymptomatic.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,5</span></a> As a result, haematological parameters are not affected, which is evidenced by its casual and late detection: most patients are in their 70s. The quantification of HbA<span class="elsevierStyleInf">1c</span> has not been affected either and, thus, there is no interference with glucose control.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The Hb Burgos percentage in heterozygosis, as it is a variant of the α chain, should be 25%, approximately. However, it is slightly lower (13–17%), both by means of ion-exchange HPLC and capillary electrophoresis, which could be due to the lower expression rate of gene <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span> compared to gene <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span>.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> As a matter of fact, gene <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span> contains HbG-Waimanalo (α<span class="elsevierStyleInf">2</span>64(E13)Asp>Asn; HBA2:c.193G>A), which has the same mutation and, still, the anomalous Hb percentage, in heterozygosis, oscillates between 17 and 22%.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In the case of homozygosis, there could be room for confusion, since it is separated from the HbS window by means of ion-exchange HPLC. Nevertheless, by means of zonal capillary electrophoresis, HbS appears in Z5, while Hb Burgos separates at Z6. Additionally, the percentage (34.3%) could lead to confusion; however, reversed phase HPLC contributes to proving that it is not a β chain variant, but rather a α variant, since only β and α chains separate globins, although judging by their homozygosis condition, higher levels should be expected (40–50%). This would confirm the fact that gene <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span> has a lower rate of expression compared to gene <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span>.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The presence of a α chain variant leads to the formation of its respective HbX<span class="elsevierStyleInf">2</span> (α<span class="elsevierStyleInf">2</span><span class="elsevierStyleSup">X</span>δ<span class="elsevierStyleInf">2</span>), contributing to a reduction in HbA<span class="elsevierStyleInf">2</span>. In some cases, this new variant could be separated, like in HbG-Philadelphia.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> In the case of Hb Burgos, both by means of ion-exchange HPLC (peak adjacent to Hb Burgos) and by zonal capillary electrophoresis (Z1), there is a reduction in the levels of Hb Burgos<span class="elsevierStyleInf">2</span> and of HbA<span class="elsevierStyleInf">2</span>, ranging between 1.1 and 2.2%. In this way, the lower the chain α synthesis, the lower the HbA<span class="elsevierStyleInf">2</span> percentage shall be, which accounts for the 1.1% evidenced by the Hb Burgos homozygote case.</p><p id="par0085" class="elsevierStylePara elsevierViewall">It has been observed that the ion-exchange HPLC is the best technique to quantify HbA<span class="elsevierStyleInf">1c</span>, and considering that it is the <span class="elsevierStyleItalic">gold standard</span> technique for Hb separation, identification of new variants in addition to the existing ones has increased.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">8,9</span></a> A study conducted in 2009, at the Hospital Clínico San Carlos hospital, on the diabetic population, showed a 2% Hb variants incidence. This has made it necessary to review the chromatograms in order to detect possible interferences at the time of quantifying glucose levels, which could lead to preventing detection of HbA<span class="elsevierStyleInf">1c</span>, as in Hb Porto Alegre,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> to undervalue it, as in Sevilla,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> HbD,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Hb Las Palmas,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> HbN-Baltimore,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> and Hb Jerez,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> or even to overestimate the HbA percentages<span class="elsevierStyleInf">1c</span>, which results in failed treatment, and the all the inconveniences it entails. Notwithstanding, since there are over 1000 different variants of Hd, many of which are rare, it is necessary to pay special attention when it comes to measuring HbA<span class="elsevierStyleInf">1</span>.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors state they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres548881" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec566596" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres548880" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec566597" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-02-17" "fechaAceptado" => "2014-07-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec566596" "palabras" => array:4 [ 0 => "Structural haemoglobinopathy" 1 => "Glycated haemoglobin" 2 => "Sequencing" 3 => "Diabetes mellitus" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec566597" "palabras" => array:4 [ 0 => "Hemoglobinopatía estructural" 1 => "Hemoglobina glucosilada" 2 => "Secuenciación" 3 => "Diabetes mellitus" ] ] ] ] "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">The glycated haemoglobin (HbA<span class="elsevierStyleInf">1c</span>) test by high performance liquid chromatography is a useful tool for the follow-up of diabetes mellitus patients. Some structural haemoglobin (Hb) variants are known to cause interference in the analytical measurement of HbA<span class="elsevierStyleInf">1c</span>.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In this study, it has been characterized a new Hb variant in 4 patients during their regular control of HbA<span class="elsevierStyleInf">1c</span>.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Selective <span class="elsevierStyleItalic">α</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span> gene sequencing showed a mutation GAC>AAC at codon 64 within exon 2. This produces a change of aspartic acid (Asp) by asparagine (Asn) that does not produce any functional alteration so the resultant molecule behaves as a silent haemoglobinopathy.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The structural Hb variants can be detected during the analysis of HbA<span class="elsevierStyleInf">1c</span> and may alter its values. Though rare, this occurrence signals the need to being aware when measuring HbA<span class="elsevierStyleInf">1c</span>.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El control de la diabetes mellitus se realiza mediante la determinación de hemoglobina glucosilada (HbA<span class="elsevierStyleInf">1c</span>) por cromatografía líquida de alta resolución. Algunas variantes estructurales de la hemoglobina (Hb) son conocidas por causar interferencia analítica en la medición de la HbA<span class="elsevierStyleInf">1c</span>.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En este estudio se ha caracterizado una nueva variante de Hb en 4 pacientes, que se detectó al realizarse un control de HbA<span class="elsevierStyleInf">1c</span>.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La secuenciación selectiva del gen <span class="elsevierStyleItalic">α1</span> mostró una mutación responsable del cambio de ácido aspártico (Asp) por asparagina (Asn) en el codón 64. El cambio de Asp por Asn no produce ninguna alteración funcional de la Hb y se comporta como una hemoglobinopatía silente.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Las variantes estructurales de la Hb se pueden detectar durante la medición de la HbA<span class="elsevierStyleInf">1c</span> y pueden alterar sus valores. Estos casos, aunque poco frecuentes, requieren examinar a fondo los cromatogramas para detectar posibles interferencias.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: de la Fuente-Gonzalo F, Martínez Nieto J, Torrejón MJ, Mayor LA, Velasco D, González Fernández FA, et al. Hb Burgos (α<span class="elsevierStyleInf">1</span> CD64(E13)(Asp→Asn)): una nueva variante de hemoglobina detectada durante la monitorización de pacientes con diabetes. Med Clin (Barc). 2015;144:26–29.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2351 "Ancho" => 3250 "Tamanyo" => 234241 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(A) <span class="elsevierStyleItalic">Hb glycosylated HPLC</span>: the Hb Burgos separates by means of glycosylated Hb, and is slower than HbA and HbA<span class="elsevierStyleInf">1c</span>. A 17.1% of the variant was obtained by this method. (B) <span class="elsevierStyleItalic">Hb capillary electrophoresis</span>: the Hb Burgos separates by means of electrophoresis and migrates between mean levels of HbA and HbA<span class="elsevierStyleInf">2</span>. An 18% of the variant was obtained by this method. (C) <span class="elsevierStyleItalic">Hb HPLC</span>: the Hb Burgos is a slower variant than Hb normal, and is located by HbS. For heterozygous cases, a percentage between 13 and 17% of this variant was obtained, and for homozygotes, the percentage obtained was 34.3%. (D) <span class="elsevierStyleItalic">Chain HPLC:</span> the Hb Burgos is a α variant, but does not separate by chain HPLC, since it has the same mobility as the normal α chain. Hb: haemoglobin; HPLC: high performance liquid chromatography.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2331 "Ancho" => 3251 "Tamanyo" => 368625 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">(A) Direct sequencing: Hb Burgos (α<span class="elsevierStyleInf">1</span> 64 (E13) Asp→Asn):GAC→AAC in heterozygous state. (B) Direct sequencing: Hb Burgos (α<span class="elsevierStyleInf">1</span> 64(E13) Asp→Asn):GAC→AAC in homozygote state. Hb: haemoglobin.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">B: Burgos; Hb: haemoglobin; MCH: mean corpuscular haemoglobin; M: male; MCV: mean corpuscular volume.</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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hb (g/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MCV (fl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MCH (pg) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HbA<span class="elsevierStyleInf">2</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HbF (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HbX<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">αα<span class="elsevierStyleSup">B</span>/αα \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">αα<span class="elsevierStyleSup">B</span>/αα \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">αα<span class="elsevierStyleSup">B</span>/αα \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">αα<span class="elsevierStyleSup">B</span>/αα<span class="elsevierStyleSup">B</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab886683.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Percentage by high performance liquid chromatography Variant™.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Haematological and genotype parameters for study subjects.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Standards of medical care in diabetes – 2008" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "American Diabetes Association" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc08-S012" "Revista" => array:7 [ "tituloSerie" => "Diabetes Care" "fecha" => "2008" "volumen" => "31" "numero" => "Suppl. 1" "paginaInicial" => "S12" "paginaFinal" => "S54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18165335" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A review of variant hemoglobins interfering with hemoglobin A1c measurement" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.R. Little" 1 => "W.L. Roberts" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Diabetes Sci Technol" "fecha" => "2009" "volumen" => "3" "paginaInicial" => "446" "paginaFinal" => "451" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20144281" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemoglobina Stanleyville II (α78(EF7)Asn→Lys). Primer caso descrito en España" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F.A. González" 1 => "P. Ropero" 2 => "S. de la Iglesia" 3 => "M. Polo" 4 => "C. Benavente" 5 => "A. Villegas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2008" "volumen" => "131" "paginaInicial" => "463" "paginaFinal" => "465" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haemoglobin Q India (alpha 64(E13) aspartic acid histidine) associated with beta-thalassemia observed in three Sindhi families" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P.K. Sukumaran" 1 => "S.M. Merchant" 2 => "M.P. Desai" 3 => "B.G. Wiltshire" 4 => "H. Lehmann" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "1972" "volumen" => "9" "paginaInicial" => "436" "paginaFinal" => "442" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4646552" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapid molecular characterization of Hb Queens and Hb Siam: two variants easily misidentified as sickle Hb" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Fucharoen" 1 => "S. Singsanan" 2 => "A. Hama" 3 => "G. Fucharoen" 4 => "K. Sanchaisuriya" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2006.08.008" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2007" "volumen" => "40" "paginaInicial" => "137" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17014836" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemoglobin G Waimanalo: alpha-64 Asp leads to Asn" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R.Q. Blackwell" 1 => "R.T. Jim" 2 => "T.G. Tan" 3 => "M.I. Weng" 4 => "C.S. Liu" 5 => "C.L. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochim Biophys Acta" "fecha" => "1973" "volumen" => "322" "paginaInicial" => "27" "paginaFinal" => "33" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4744336" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variant haemoglobins. A guide to identification" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.J. Bain" 1 => "B.J. Wild" 2 => "A.D. Stephens" 3 => "L. Phelan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2010" "editorial" => "Wiley-Blackwell" "editorialLocalizacion" => "Oxford" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advantages in the use of high performance liquid chromatography technique for screening hemoglobinopathies in Venezuela" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Bravo-Urquiola" 1 => "A. Arends" 2 => "S. Montilla" 3 => "D. Velásquez" 4 => "G. Garcia" 5 => "M. Alvarez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Invest Clin" "fecha" => "2004" "volumen" => "45" "paginaInicial" => "309" "paginaFinal" => "315" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15602897" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N.M. Nasir" 1 => "M. Thevarajah" 2 => "C.Y. Yean" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0973-3930.62598" "Revista" => array:6 [ "tituloSerie" => "Int J Diabetes Dev Ctries" "fecha" => "2010" "volumen" => "30" "paginaInicial" => "86" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20535312" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of hemoglobin Porto Alegre on glycated hemoglobin (HbA(1c)) measurement with the HA-8160 high performance liquid chromatography method" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Lorenzo-Medina" 1 => "S. de-la-Iglesia" 2 => "P. Ropero" 3 => "A. Martín-Aguila" 4 => "L. Ruiz-García" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/cclm-2013-0049" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2013" "volumen" => "51" "paginaInicial" => "e247" "paginaFinal" => "e249" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23612667" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemoglobin Seville [α2 β2 81(EF5) Leu→Phe] a silent phenotypic variant that interferes in hemoglobin A1c measurement by ion-exchange HPLC method" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.H. Del Rey" 1 => "M. Conde-Sánchez" 2 => "P. Ropero-Gradilla" 3 => "I. Domínguez-Pascual" 4 => "F.A. González-Fernández" 5 => "A. Villegas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2011.04.007" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2011" "volumen" => "44" "paginaInicial" => "933" "paginaFinal" => "935" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21554865" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interference of hemoglobin D on measurements of hemoglobin A1c by the high-performance liquid chromatography HA-8160 in 27 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Lorenzo-Medina" 1 => "S. de-la-Iglesia" 2 => "P. Ropero" 3 => "R. Martin-Alfaro" 4 => "L. Quintana-Hidalgo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Diabetes Sci Technol" "fecha" => "2012" "volumen" => "6" "paginaInicial" => "1235" "paginaFinal" => "1237" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23063052" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interference of hemoglobin (Hb) Las Palmas with HPLC measurement of HbA(1c) in 87 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Lorenzo-Medina" 1 => "S.D. La Iglesia" 2 => "P. Ropero" 3 => "M. Navarro-Romero" 4 => "R. Mart N-Alfaro" 5 => "S.C. Guindeo-Casas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/cclm.2012.780" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2011" "volumen" => "50" "paginaInicial" => "403" "paginaFinal" => "405" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22718637" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interference of hemoglobin (Hb) N-Baltimore on measurement of HbA(1c) using the HA-8160 HPLC method" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Lorenzo-Medina" 1 => "S. de-la-Iglesia" 2 => "P. Ropero" 3 => "P. Nogueira-Salgueiro" 4 => "A. Martin-Aguila" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2013" "volumen" => "51" "paginaInicial" => "e13" "paginaFinal" => "e15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23641500" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemoglobin Jerez [α2 β2 95 (FG2) Lys→Gln]: Performance of HbA1c measurement with five analytical methods" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.L. González-Borrachero" 1 => "P. Ropero-Gradilla" 2 => "J.M. Vergara-Chozas" 3 => "F.A. González-Fernández" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cca.2013.07.022" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2013" "volumen" => "425" "paginaInicial" => "160" "paginaFinal" => "162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23906795" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014400000001/v1_201509042040/S2387020615000078/v1_201509042040/en/main.assets" "Apartado" => array:4 [ "identificador" => "43315" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Clinical report" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014400000001/v1_201509042040/S2387020615000078/v1_201509042040/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020615000078?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2017 October | 11 | 0 | 11 |
| 2017 September | 19 | 3 | 22 |
| 2017 August | 5 | 4 | 9 |
| 2017 July | 8 | 2 | 10 |
| 2017 June | 4 | 2 | 6 |
| 2017 May | 2 | 9 | 11 |
| 2017 April | 7 | 2 | 9 |
| 2017 March | 4 | 2 | 6 |
| 2017 February | 13 | 4 | 17 |
| 2017 January | 3 | 0 | 3 |
| 2015 November | 1 | 0 | 1 |
