Defectos de la fosforilación oxidativa de presentación neonatal: revisión casuística
Oxidative Phosphorilation Defects With Neonatal Presentation: Review Of Our Experience
V. Rebage Moisésa,*, S. Rite Graciaa, J. López-Pisónb, M. Muñoz Albillosa, E. Aisa Pardoa, J.A. Giménez Másc, J. Arenas Barberod, J. Montoya Vilarroyae, A. Marco Telloa, M.I. Salazar García-Blancof, A. Baldellou Vázquezg
a Unidad Neonatal. Hospital Miguel Servet.Zaragoza
b Sección de Neuropediatría. Hospital Miguel Servet.Zaragoza
c Servicio de Anatomía Patológica. Hospital Miguel Servet.Zaragoza
d Centro de Investigación. Hospital 12 de Octubre. Madrid
e Departamento de Bioquímica y Biología Molecular y Celular. Universidad de Zaragoza
f Laboratorio de Bioquímica. Hospital Miguel Servet. de Zaragoza
g Unidad de Metabolismo. Hospital Miguel Servet. de Zaragoza
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Hospital Miguel Servet. de Zaragoza" "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Correspondencia: Princesa, 11-13, 3.° A. 50005 Zaragoza" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Oxidative Phosphorilation Defects With Neonatal Presentation: Review Of Our Experience" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "1999-08-31" "fechaAceptado" => "1999-12-31" "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec186244" "palabras" => array:4 [ 0 => "Mitocondria" 1 => "Recién nacido" 2 => "Defectos de la fosforilación oxidativa" 3 => "Encefalopatía mitocondrial" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Definir el síndrome de déficit de la fosforilación oxidativa neonatal, en función de su incidencia, características perinatales, clínicas, bioquímicas y genéticas.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se revisan los casos de 9 recién nacidos catalogados como déficit de la fosforilación oxidativa en los últimos 8 años en nuestro centro, mediante valoración clínica, metabólica, histopatológica, enzimática y molecular, además de otras evaluaciones. El diagnóstico se estableció en función del déficit enzimático de la cadena respiratoria, asociadoa alteraciones del ADNmt en un caso, y en cinco a anomalías ultraestructurales mitocondriales.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La incidencia fue de 1/3.555 y de 1/832 recién nacidosingresados en nuestra unidad neonatal. Cuatro tenían antecedentes familiares positivos, y dos polihidramnios. La mayoría (8/9) fueron recién nacidos a término, de embarazo y parto normales, con Apgar y somatometría también normales. La clínica se inició en el período neonatal inmediato, como sufrimiento neurológico agudo en la mayoría. La evolución fue grave (5 fallecieron y 4 sobreviven gravemente afectados). Todos presentaban un fenotipo clínico de encefalopatía grave precoz, asociada a dismorfia, hipotonía, alteraciones neurosensoriales, atrofia y disgenesia cerebral, electroencefalograma patológico, y en 5 de ellos, además, a anomalías viscerales (principalmente cardiopatía). La alteración bioquímica más frecuente fue un aumento significativo del cociente lactato/piruvato. Cinco pacientes presentaron alteraciones ultraestructurales mitocondriales en la biopsia muscular pero la tinción de Cox no resultó claramente patológica en ningún caso. Tres tenían un déficit del complejo IV, tres de I-IV, dos del I y uno del I-IIIIV. Sólo en un paciente se detectaron deleciones múltiples del ADNmt.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Se trata de enfermedades frecuentes y graves, de comienzo prenatal con escasa repercusión fetal, fenotipo clínico homogéneo con afectación predominante del SNC y extraneurológica variable, y perfil bioquímico inconstante. El diagnóstico exige el estudio enzimático de la cadenarespiratoria en todos los casos sospechosos.</p>" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To define the oxidative phosporilation deficit syndrome in the neonatal in terms of incidence and clinical, biochemical and genetic features.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We report 9 newborns diagnosed as oxidatic phosporilation deficit during the last 8 years in our hospital by means of clinical, metabolic, pathological and molecular studies, among other evaluations. The diagnosis was established based on ensymatic deficit of the respiratory chain, associated with alterations in the mtDNA in one case, and with mitochondrial ultrastructural anomalies in 5 cases.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">There was an incidence of 1/3.555 newborns and 1/832 newborns admitted in our Neonatal Unit. In four of them there were familial antecedents and polihidramnios in two. Most of them, 8 out of 9, were born at term after anormal pregnancy and delivery, with normal Apgar score and auxological examination. Symptomatology started immediately at the neonatal period as acute neurological damage in most of them. There was a severe evolution as 5 children died and 4 survived with severe damage. All of them had the classical phenotype of early severe encefalopathy, associated with dismorphicfeatures, hypotomía, neurosensorial defects, brain dysgenesis and atrophy, anomalies in the EEG and in 5 of therm there were also systemic anomalies, mainly cardiopathy. The most freqyent biochemicalalteration was a significative increment of the quotient lactate/piruvate. Five patients presented ultrastructural alterations of the mitochondria in thr musclebiopsy but Cox stain was not positive in any case.three cases has a deficit of the complex IV, e of the complex I-IV, 2 of the complex I and one the complex I-III-IV.Only one patient had multiple deletions in the mtDNA.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Oxidatic phosporilation deficit are frequent and severe diseases of prenatal onset with limited fetal effects, homobeneous clinical phenotipe with frequent damage of the central nervous system and variable extraneurological alteration and inconsistent biochemical pattern. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 6 | 10 | 16 |
| 2024 Octubre | 57 | 59 | 116 |
| 2024 Septiembre | 51 | 38 | 89 |
| 2024 Agosto | 58 | 78 | 136 |
| 2024 Julio | 39 | 46 | 85 |
| 2024 Junio | 45 | 43 | 88 |
| 2024 Mayo | 42 | 40 | 82 |
| 2024 Abril | 51 | 35 | 86 |
| 2024 Marzo | 34 | 53 | 87 |
| 2024 Febrero | 49 | 51 | 100 |
| 2024 Enero | 51 | 37 | 88 |
| 2023 Diciembre | 35 | 30 | 65 |
| 2023 Noviembre | 32 | 44 | 76 |
| 2023 Octubre | 37 | 42 | 79 |
| 2023 Septiembre | 31 | 28 | 59 |
| 2023 Agosto | 28 | 17 | 45 |
| 2023 Julio | 24 | 45 | 69 |
| 2023 Junio | 33 | 29 | 62 |
| 2023 Mayo | 43 | 28 | 71 |
| 2023 Abril | 22 | 18 | 40 |
| 2023 Marzo | 46 | 26 | 72 |
| 2023 Febrero | 21 | 21 | 42 |
| 2023 Enero | 27 | 32 | 59 |
| 2022 Diciembre | 72 | 22 | 94 |
| 2022 Noviembre | 62 | 48 | 110 |
| 2022 Octubre | 33 | 47 | 80 |
| 2022 Septiembre | 40 | 65 | 105 |
| 2022 Agosto | 37 | 57 | 94 |
| 2022 Julio | 31 | 39 | 70 |
| 2022 Junio | 26 | 37 | 63 |
| 2022 Mayo | 41 | 43 | 84 |
| 2022 Abril | 41 | 53 | 94 |
| 2022 Marzo | 36 | 49 | 85 |
| 2022 Febrero | 27 | 35 | 62 |
| 2022 Enero | 41 | 37 | 78 |
| 2021 Diciembre | 19 | 62 | 81 |
| 2021 Noviembre | 34 | 84 | 118 |
| 2021 Octubre | 46 | 45 | 91 |
| 2021 Septiembre | 34 | 52 | 86 |
| 2021 Agosto | 34 | 46 | 80 |
| 2021 Julio | 23 | 56 | 79 |
| 2021 Junio | 29 | 47 | 76 |
| 2021 Mayo | 46 | 27 | 73 |
| 2021 Abril | 118 | 87 | 205 |
| 2021 Marzo | 90 | 24 | 114 |
| 2021 Febrero | 61 | 29 | 90 |
| 2021 Enero | 42 | 25 | 67 |
| 2020 Diciembre | 49 | 25 | 74 |
| 2020 Noviembre | 29 | 10 | 39 |
| 2020 Octubre | 41 | 15 | 56 |
| 2020 Septiembre | 38 | 18 | 56 |
| 2020 Agosto | 32 | 5 | 37 |
| 2020 Julio | 38 | 14 | 52 |
| 2020 Junio | 25 | 12 | 37 |
| 2020 Mayo | 46 | 28 | 74 |
| 2020 Abril | 53 | 26 | 79 |
| 2020 Marzo | 31 | 17 | 48 |
| 2020 Febrero | 44 | 20 | 64 |
| 2020 Enero | 36 | 18 | 54 |
| 2019 Diciembre | 54 | 29 | 83 |
| 2019 Noviembre | 32 | 14 | 46 |
| 2019 Octubre | 19 | 9 | 28 |
| 2019 Septiembre | 37 | 23 | 60 |
| 2019 Agosto | 25 | 13 | 38 |
| 2019 Julio | 29 | 30 | 59 |
| 2019 Junio | 46 | 23 | 69 |
| 2019 Mayo | 41 | 48 | 89 |
| 2019 Abril | 48 | 20 | 68 |
| 2019 Marzo | 21 | 14 | 35 |
| 2019 Febrero | 22 | 5 | 27 |
| 2019 Enero | 30 | 15 | 45 |
| 2018 Diciembre | 24 | 16 | 40 |
| 2018 Noviembre | 35 | 7 | 42 |
| 2018 Octubre | 74 | 14 | 88 |
| 2018 Septiembre | 20 | 2 | 22 |
| 2018 Julio | 2 | 0 | 2 |
| 2018 Junio | 1 | 0 | 1 |
| 2018 Mayo | 4 | 0 | 4 |
| 2018 Abril | 9 | 0 | 9 |
| 2018 Marzo | 12 | 0 | 12 |
| 2018 Febrero | 3 | 0 | 3 |
| 2018 Enero | 7 | 0 | 7 |
| 2017 Diciembre | 13 | 0 | 13 |
| 2017 Noviembre | 7 | 0 | 7 |
| 2017 Octubre | 8 | 1 | 9 |
| 2017 Septiembre | 7 | 0 | 7 |
| 2017 Agosto | 4 | 0 | 4 |
| 2017 Julio | 6 | 1 | 7 |
| 2017 Junio | 19 | 20 | 39 |
| 2017 Mayo | 14 | 14 | 28 |
| 2017 Abril | 12 | 8 | 20 |
| 2017 Marzo | 9 | 41 | 50 |
| 2017 Febrero | 4 | 14 | 18 |
| 2017 Enero | 5 | 8 | 13 |
| 2016 Diciembre | 14 | 22 | 36 |
| 2016 Noviembre | 31 | 14 | 45 |
| 2016 Octubre | 32 | 15 | 47 |
| 2016 Septiembre | 26 | 11 | 37 |
| 2016 Agosto | 25 | 7 | 32 |
| 2016 Julio | 14 | 5 | 19 |
| 2016 Marzo | 1 | 0 | 1 |
| 2016 Febrero | 2 | 0 | 2 |
| 2015 Diciembre | 2 | 0 | 2 |
| 2015 Julio | 7 | 0 | 7 |
| 2015 Junio | 8 | 0 | 8 |
| 2015 Mayo | 19 | 0 | 19 |
| 2015 Abril | 12 | 0 | 12 |
| 2015 Marzo | 4 | 0 | 4 |
| 2015 Febrero | 3 | 0 | 3 |
| 2015 Enero | 3 | 0 | 3 |
| 2014 Diciembre | 6 | 0 | 6 |
| 2014 Noviembre | 12 | 0 | 12 |
| 2014 Octubre | 8 | 0 | 8 |
| 2014 Septiembre | 5 | 0 | 5 |
| 2014 Agosto | 10 | 0 | 10 |
| 2014 Julio | 14 | 0 | 14 |
| 2014 Junio | 17 | 0 | 17 |
| 2014 Mayo | 22 | 0 | 22 |
| 2014 Abril | 22 | 0 | 22 |
| 2014 Marzo | 20 | 0 | 20 |
| 2014 Febrero | 17 | 0 | 17 |
| 2014 Enero | 9 | 0 | 9 |
| 2013 Diciembre | 20 | 0 | 20 |
| 2013 Noviembre | 12 | 0 | 12 |
| 2013 Octubre | 23 | 0 | 23 |
| 2013 Septiembre | 12 | 0 | 12 |
| 2013 Agosto | 7 | 0 | 7 |
| 2013 Julio | 7 | 0 | 7 |
| 2013 Junio | 3 | 0 | 3 |
| 2013 Mayo | 4 | 0 | 4 |
| 2013 Abril | 3 | 0 | 3 |
| 2013 Marzo | 5 | 0 | 5 |
| 2013 Febrero | 18 | 0 | 18 |
| 2013 Enero | 5 | 0 | 5 |
| 2012 Diciembre | 8 | 0 | 8 |
| 2012 Noviembre | 3 | 0 | 3 |
| 2012 Octubre | 1 | 0 | 1 |
| 2012 Septiembre | 5 | 0 | 5 |
| 2012 Agosto | 4 | 0 | 4 |
| 2000 Marzo | 3260 | 0 | 3260 |
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