Déficit de alfa-1-antitripsina en España (variantes deficientes PI*S y PI*Z): prevalencia estimada y número de sujetos calculados para cada fenotipo
PI*S and PI*Z alpha 1-antitrypsin deficiency: estimated prevalence and number of deficient subjects in spain
Ignacio Blancoa,
, Enrique Fernández-Bustillob, Frederick J. de Serresc, Daniel Alkassamd, Carmen Rodríguez Menéndeze
Autor para correspondencia
ignacio.blanco@sespa.princast.es
Sección de Neumología. Servicio de Medicina Interna.Hospital Valle del Nalón.Polígono de Riaño, s/n. 33194 Riaño.Principado de Asturias. España.Correo electrónico
Sección de Neumología. Servicio de Medicina Interna.Hospital Valle del Nalón.Polígono de Riaño, s/n. 33194 Riaño.Principado de Asturias. España.Correo electrónico
a Sección de Neumología. Servicio de Medicina Interna. Hospital Valle del Nalón. Langreo. Principado de Asturias
b Unidad de Bioestadística. Hospital Universitario Central de Asturias. Oviedo. Principado de Asturias
c Laboratory of Molecular Toxicology. Environmental Toxicology Program.National Institute of Environmental Health Sciences. Chapel Hill. North Carolina. EE.UU
d Servicio de Análisis Clínicos. Hospital Valle del Nalón. Langreo. Principado de Asturias
e Servicio de Análisis Clínicos. Instituto Nacional de Silicosis. Hospital Universitario Central de Asturias.Oviedo. Principado de Asturias. España
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"apellidos" => "de Serres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Daniel" "apellidos" => "Alkassam" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Carmen" "apellidos" => "Rodríguez Menéndez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Sección de Neumología. Servicio de Medicina Interna. Hospital Valle del Nalón. Langreo. Principado de Asturias" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Bioestadística. Hospital Universitario Central de Asturias. Oviedo. Principado de Asturias" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Laboratory of Molecular Toxicology. Environmental Toxicology Program.National Institute of Environmental Health Sciences. Chapel Hill. North Carolina. EE.UU" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Análisis Clínicos. Hospital Valle del Nalón. Langreo. Principado de Asturias" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Análisis Clínicos. Instituto Nacional de Silicosis. Hospital Universitario Central de Asturias.Oviedo. Principado de Asturias. España" "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Sección de Neumología. Servicio de Medicina Interna.Hospital Valle del Nalón.Polígono de Riaño, s/n. 33194 Riaño.Principado de Asturias. España.Correo electrónico" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "PI<span class="elsevierStyleSup">*</span>S and PI<span class="elsevierStyleSup">*</span>Z alpha 1-antitrypsin deficiency: estimated prevalence and number of deficient subjects in spain" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2004-02-16" "fechaAceptado" => "2004-07-27" "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec222457" "palabras" => array:5 [ 0 => "Alfa-1-antitripsina" 1 => "Déficit de alfa-1-antitripsina" 2 => "Fenotipos PI" 3 => "Epidemiología genética" 4 => "España" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec222458" "palabras" => array:5 [ 0 => "Alpha 1-antitrypsin" 1 => "Alpha 1-antitrypsin deficiency" 2 => "PI phenotypes" 3 => "Genetic epidemiology" 4 => "Spain" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Fundamento y objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El déficit de alfa-1-antitripsina (DAAT) es un trastorno hereditario conun riesgo incrementado de padecer enfisema pulmonar y hepatopatías crónicas en niños yadultos. Actualmente existe en España la posibilidad de aplicar tratamiento sustitutivo a pacientescon déficit grave que cumplan los requisitos establecidos por el Registro Español dePacientes con DAAT, por lo que consideramos importante conocer el número de sujetos conDAAT en sus variantes PIS y PIZ y su distribución por fenotipos</p> <span class="elsevierStyleSectionTitle">Sujetos, material y método</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Selección de estudios publicados sobre frecuencias alélicas PIS yPIZ en poblaciones españolas, con los siguientes criterios: a) método fiable de identificaciónde fenotipos; b) no ser estudios de cribado; c) factor de precisión estadística mayor o igual a 5,y d) muestras representativas de la población general de la comunidad</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se seleccionaron 34 cohortes, que quedaron reducidas a 4 tras eliminar las que nocumplieron los criterios requeridos. Las frecuencias medias (en tanto por 1.000) fueron: 104(intervalo de confianza [IC] del 95%, 96-113) para PI<span class="elsevierStyleSup">*</span>S y 17 (IC del 95%, 14-21) para PI<span class="elsevierStyleSup">*</span>Z.Extrapolando estos datos al total de la población, calculamos que habría en España 9.173.181individuos con DAAT (IC del 95%, 9.167.966-9.178.398), con la siguiente distribución porfenotipos: PIMS, 7.358.263 (IC del 95%, 6.696.222-8.072.328); PIMZ, 1.222.041 (IC del95%, 972.767-1.539.805); PISS, 436.023 (IC del 95%, 369.057-514.244); PISZ, 144.827(IC del 95%, 107.227-195.038), y PIZZ, 12.026 (IC del 95%, 7.788-18.493). La prevalenciaglobal calculada del DAAT fue de un deficiente por cada 4,4 sujetos, con la siguiente distribución:PIMS, 1/5; PIMZ, 1/33; PISS, 1/92; PISZ, 1/278, y PIZZ, 1/3.344</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El DAAT es una enfermedad frecuente e infradiagnosticada</p>" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Background and objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Alpha-1-antitrypsin deficiency (AATD) is an hereditary disorder withincreased risk of pulmonary emphysema and chronic liver diseases in children and adults. Sinceit is possible currently in Spain to apply alpha-1-antitrypsin replacement therapy to AATDpatients, the objective of this study was to calculate the total number of subjects affected byPIS and PIZ AATD, and its phenotypic distribution</p> <span class="elsevierStyleSectionTitle">Subjects, material and method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Selection of published studies on allelic frequencies PIS and PIZaccording to the following criteria: a) alpha-1-antitrypsin phenotyping performed by isoelectrofocusing;b) rejection of »screening studies»; c) statistic precision factor score of 5, and d)samples representative of the Spanish general population</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Four out 34 cohorts were selected. Mean gene frequencies (per 1,000) were: 104(95% confidence interval [CI], 96-113) for PI<span class="elsevierStyleSup">*</span>S and 17 (95% CI, 14-21) for PI<span class="elsevierStyleSup">*</span>Z. These dataindicated that it would exist in Spain 9,173,181 AATD subjects (95% CI, 9,167,966-9,178,398), with the following phenotypic distribution: 7,358,263 (95% CI, 6,696,222-8,072,328) for PIMS; 1,222,041 (95% CI, 972,767-1,539,805) for PIMZ; 436,023 (95% CI,369,057-514,244) for PISS; 144,827 (95% CI, 107,227-195,038) for PISZ; and 12,026(95% CI, 7,788-18,493) for PIZZ. The global prevalence was 1 out of 4.4 individuals, with thefollowing distribution: PIMS 1/5; PIMZ 1/33; PISS 1/92; PISZ 1/278; and PIZZ 1/3,344</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">AATD is a frequent but underdiagnosed disease in Spain</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Referencias bibliográficas" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:50 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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| año/Mes | Html | Total | |
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| 2024 Septiembre | 0 | 23 | 23 |
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| 2024 Marzo | 0 | 38 | 38 |
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| 2024 Enero | 0 | 32 | 32 |
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| 2023 Septiembre | 0 | 23 | 23 |
| 2023 Agosto | 0 | 20 | 20 |
| 2023 Julio | 0 | 43 | 43 |
| 2023 Junio | 0 | 16 | 16 |
| 2023 Mayo | 0 | 37 | 37 |
| 2023 Abril | 0 | 13 | 13 |
| 2023 Marzo | 0 | 9 | 9 |
| 2023 Febrero | 0 | 10 | 10 |
| 2023 Enero | 0 | 10 | 10 |
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| 2020 Mayo | 0 | 8 | 8 |
| 2020 Abril | 0 | 7 | 7 |
| 2020 Marzo | 1 | 4 | 5 |
| 2020 Febrero | 0 | 18 | 18 |
| 2020 Enero | 0 | 12 | 12 |
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| 2019 Noviembre | 0 | 12 | 12 |
| 2019 Octubre | 0 | 16 | 16 |
| 2019 Septiembre | 0 | 13 | 13 |
| 2019 Agosto | 0 | 11 | 11 |
| 2019 Julio | 0 | 10 | 10 |
| 2019 Junio | 0 | 29 | 29 |
| 2019 Mayo | 1 | 50 | 51 |
| 2019 Abril | 0 | 63 | 63 |
| 2019 Marzo | 0 | 7 | 7 |
| 2019 Febrero | 0 | 5 | 5 |
| 2019 Enero | 0 | 6 | 6 |
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| 2018 Octubre | 0 | 10 | 10 |
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| 2018 Agosto | 0 | 5 | 5 |
| 2018 Mayo | 0 | 5 | 5 |
| 2018 Abril | 0 | 1 | 1 |
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| 2017 Octubre | 8 | 15 | 23 |
| 2017 Septiembre | 12 | 9 | 21 |
| 2017 Agosto | 8 | 10 | 18 |
| 2017 Julio | 14 | 25 | 39 |
| 2017 Junio | 12 | 17 | 29 |
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| 2017 Abril | 13 | 20 | 33 |
| 2017 Marzo | 20 | 48 | 68 |
| 2017 Febrero | 7 | 13 | 20 |
| 2017 Enero | 13 | 4 | 17 |
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| 2016 Noviembre | 52 | 5 | 57 |
| 2016 Octubre | 72 | 5 | 77 |
| 2016 Septiembre | 25 | 12 | 37 |
| 2016 Agosto | 11 | 9 | 20 |
| 2016 Julio | 20 | 2 | 22 |
| 2016 Junio | 39 | 8 | 47 |
| 2016 Mayo | 36 | 26 | 62 |
| 2016 Abril | 32 | 8 | 40 |
| 2016 Marzo | 38 | 11 | 49 |
| 2016 Febrero | 33 | 9 | 42 |
| 2016 Enero | 30 | 7 | 37 |
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| 2015 Noviembre | 35 | 7 | 42 |
| 2015 Octubre | 35 | 9 | 44 |
| 2015 Septiembre | 29 | 19 | 48 |
| 2015 Agosto | 47 | 4 | 51 |
| 2015 Julio | 43 | 13 | 56 |
| 2015 Junio | 28 | 4 | 32 |
| 2015 Mayo | 42 | 8 | 50 |
| 2015 Abril | 34 | 12 | 46 |
| 2015 Marzo | 30 | 8 | 38 |
| 2015 Febrero | 11 | 2 | 13 |
| 2015 Enero | 51 | 4 | 55 |
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| 2014 Noviembre | 35 | 1 | 36 |
| 2014 Octubre | 54 | 1 | 55 |
| 2014 Septiembre | 54 | 3 | 57 |
| 2014 Agosto | 52 | 3 | 55 |
| 2014 Julio | 70 | 3 | 73 |
| 2014 Junio | 66 | 1 | 67 |
| 2014 Mayo | 38 | 6 | 44 |
| 2014 Abril | 52 | 2 | 54 |
| 2014 Marzo | 41 | 1 | 42 |
| 2014 Febrero | 40 | 1 | 41 |
| 2014 Enero | 64 | 3 | 67 |
| 2013 Diciembre | 50 | 3 | 53 |
| 2013 Noviembre | 35 | 9 | 44 |
| 2013 Octubre | 51 | 4 | 55 |
| 2013 Septiembre | 35 | 1 | 36 |
| 2013 Agosto | 51 | 3 | 54 |
| 2013 Julio | 37 | 3 | 40 |
| 2013 Mayo | 1 | 0 | 1 |
| 2004 Diciembre | 1359 | 0 | 1359 |
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