Newborn Screening Program in the Community of Madrid: evaluation of positive cases
e202012185
Keywords:
Expanded newborn screening, Inborn errors of metabolism, Tandem mass spectrometry, False positiveAbstract
Background: Tandem mass spectrometry (MS/MS) is being used for newborn screening since this laboratory testing technology increases the number of metabolic disorders that can be detected from dried blood-spot specimens. In the Community of Madrid, it was implemented in March 2011 and it includes 13 aminoacidopathies, fatty acid oxidation disorders and organic acidemias. The aim of this study was to describe our experience and evaluate the screening positive cases in a period of 9 years (2011-2019).
Methods: During the period of the study, a total of 592.822 neonates were screened with this expanded program by MS/MS in the Community of Madrid. Amino acids, acylcarnitines, and succinylacetone were quantified in all samples that met the quality criteria. Means, medians, percentiles and standard deviation of the analytes and ratios of interest were calculated.
Results: 901 patients (0,15 %) with a positive screening test were referred to clinical evaluation. 230 patients were diagnosed of 30 different inborn errors of metabolism (prevalence 1:2577), 11 of which were not included as a target in the Community of Madrid newborn screening program. The global positive predictive value was 25,6 %. During this period of time, two false negative cases were detected. The most prevalent disorders were phenylketonuria/hyperphenylalaninemia and medium chain acyl-CoA dehydrogenase deficiency (1:6444 and 1:13174 respectively). 93 % of the patients were detected in the presymptomatic stage.
Conclusions: During the last 9 years a large number of cases of IEM have been detected with an acceptable global positive predictive value. These results confirm the utility of inborn errors of metabolism newborn screening as a public health program.
Downloads
References
Ferreira CR, van Karnebeek CDM, Vockley J, Blau N.
A proposed nosology of inborn errors of metabolism. Genet Med. 2019;21:102-106.
Garg U, Dasouki M. Expanded newborn screening of inherited metabolic disorders by tandem mass spectrometry: clinical and laboratory aspects. Clin Biochem. 2006;39:315-32.
Andermann A, Blancquaert I, Beauchamp S, Déry V. Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years. Bull World Health Organ. 2008;86:317-9.
Millington DS, Kodo N, Norwood DL, Roe CR. Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J Inherit Metab Dis. 1990;13:321-4.
Therrell BL, Padilla CD, Loeber JG, Kneisser I, Saadallah A, Borrajo GJC et al. Current status of newborn screening worldwide: 2015. Semin Perinatol. 2015;39:171-87.
Programas de Cribado Neonatal en España: Actualización y propuestas de futuro. Documento consenso. Real Patronato sobre Discapacidad. Ministerio de Sanidad y Política Social, 2010.
Castiñeiras DE, Couce ML, Marín JL, González-Lamuño D, Rocha H. Situación actual del cribado neonatal de enfermedades metabólicas en España y en el mundo. An Pediatr (Barc). 2019;91:128.e1-128.e14.
Clinical and Laboratory Standards Institute (CLSI). Newborn Screening by Tandem Mass Spectrometry; Approved Guideline. CLSI document NBS04-AEd2. Wayne, PA: CLSI, 2017.
Juan-Fita MJ, Egea-Mellado JM, González-Gallego I, Moya-Quiles MR, Fernández-Sánchez A. Cribado neonatal ampliado en la Región de Murcia. Experiencia de tres años. Med Clin (Barc). 2012;139:566-71.
Vilarinho L, Rocha H, Sousa C, Marcão A, Fonseca H, Bogas M, Osório RV. Four years of expanded newborn screening in Portugal with tandem mass spectrometry. J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S133-8.
La Marca G, Malvagia S, Casetta B, Pasquini E, Donati MA, Zammarchi E. Progress in expanded newborn screening for metabolic conditions by LC-MS/MS in Tuscany: update on methods to reduce false tests. J Inherit Metab Dis. 2008;31:S395-404.
Loukas YL, Soumelas GS, Dotsikas Y, Georgiou V, Molou E, Thodi G, Boutsini M, Biti S, Papadopoulos K. Expanded newborn screening in Greece: 30 months of experience. J Inherit Metab Dis. 2010;33:S341-8.
Watson MS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell RR and American College of Medical Genetics Newborn Screening Expert Group. Newborn screening: toward a uniform screening panel and system--executive summary. Pediatrics. 2006;117:S296-30.
Anikster Y, Haack TB, Vilboux T, Pode-Shakked B, Thöny B, Shen N et al. Biallelic mutations in DNAJC12 cause hyperphenylalaninemia, hystonia, and intellectual disability. Am J Hum Genet. 2017;100:257-266.
Gallego D, Leal F, Gámez A, Castro M, Navarrete R, Sanchez-Lijarcio O et al. Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. Hum Mutat. 2020;41:1329-1338.
Knerr I, Colombo R, Urquhart J, Morais A, Merinero B, Oyarzabal A et al. Expanding the genetic and phenotypic spectrum of branched-chain amino acid transferase 2 deficiency. J Inherit Metab Dis. 2019 Sep;42(5):809-817.
Kronn D. Navigating Newborn Screening in the NICU: A User’s Guide. NeoReviews, 2019; 20: e280-e291
Shoraka HR, Haghdoost AA, Baneshi MR, Bagherinezhad Z, Zolala F. Global prevalence of classic phenylketonuria based on Neonatal Screening Program Data: systematic review and meta-analysis. Clin Exp Pediatr. 2020;63:34-43.
Rocha H, Castiñeiras D, Delgado C, Egea J, Yahyaoui R, González Y et al. Birth prevalence of fatty acid β-oxidation disorders in Iberia.JIMD Rep. 2014;16:89-94.
Fernández Ruano ML, Besga García B, Montero Plata A, Dulín Íñiguez E. Falsos positivos en cribado neonatal: elevación de C5-carnitina en neonatos por tratamiento preparto con cefditoreno pivoxilo. Rev Esp Salud Publica. 2018 Jun 4;92:e201806025.
Landau YE, Waisbren SE, Chan LMA, Levy HL. Long-term outcome of expanded newborn screening at Boston children’s hospital: benefits and challenges in defining true disease. J Inherit Metab Dis. 2017;40:209-218.
Kwon JM. Testing for Inborn Errors of Metabolism. Continuum (Minneap Minn). 2018;24:37-56.
Rinaldo P, Zafari S, Tortorelli S, Matern D. Making the case for objective performance metrics in newborn screening by tandem mass spectrometry. Ment Retard Dev Disabil Res Rev. 2006;12:255-61.
Lindner M, Ho S, Kölker S, Abdoh G, Hoffmann GF, Burgard P. Newborn screening for methylmalonic acidurias--optimization by statistical parameter combination. J Inherit Metab Dis. 2008;31:379-85
Monostori P, Klinke G, Richter S, Baráth Á, Fingerhut R, Baumgartner MR et al. Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders. PLoS One. 2017;12:e0184897.
Malvagia S, Haynes CA, Grisotto L, Ombrone D, Funghini S, Moretti E et al. Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias. Clin Chim Acta. 2015 Oct 23;450:342-8.
Stanescu S, Belanger-Quintana A, Fernández-Felix BM, Pérez-Cerdá C, Merinero B, Ruiz-Salas P et al. Long-term follow-up with filter paper samples in patients with propionic acidemia. JIMD Reports. 2020;1–8.
Downloads
Published
How to Cite
License
Copyright (c) 2020 Ana Cambra Conejero, Laura Martínez Figueras, Alicia Ortiz Temprado, Paula Blanco Soto, Álvaro Martín Rivada, Laura Palomino Pérez, Elvira Cañedo Villarroya, Consuelo Pedrón Giner, Pilar Quijada Fraile, Elena Martín-Hernández, María Teresa García Silva, Silvia Chumillas Calzada, Marcello Bellusci, Amaya Belanger-Quintana, Sinziana Stanescu, Mercedes Martínez-Pardo Casanova, Ana Moráis López, Ana Bergua Martínez, Pedro Ruiz-Salas, Belén Pérez González, Magdalena Ugarte, Miguel L.F. Ruano
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Usted es libre de:
Compartir — copiar y redistribuir el material en cualquier medio o formato.
La licenciante no puede revocar estas libertades en tanto usted siga los términos de la licencia.
Bajo los siguientes términos:
Atribución — Usted debe dar crédito de manera adecuada , brindar un enlace a la licencia, e indicar si se han realizado cambios. Puede hacerlo en cualquier forma razonable, pero no de forma tal que sugiera que usted o su uso tienen el apoyo de la licenciante.
NoComercial — Usted no puede hacer uso del material con propósitos comerciales.
SinDerivadas — Si remezcla, transforma o crea a partir del material, no podrá distribuir el material modificado.
No hay restricciones adicionales — No puede aplicar términos legales ni medidas tecnológicas que restrinjan legalmente a otras a hacer cualquier uso permitido por la licencia.
Avisos:
No tiene que cumplir con la licencia para elementos del material en el dominio público o cuando su uso esté permitido por una excepción o limitación aplicable.
No se dan garantías. La licencia podría no darle todos los permisos que necesita para el uso que tenga previsto. Por ejemplo, otros derechos como publicidad, privacidad, o derechos morales pueden limitar la forma en que utilice el material.
![¿Cómo evaluar para la RESP? [PARA REVISORES]](https://ojs.sanidad.gob.es/public/site/images/rmartinb/pastilla-revisores-0eaa113abcbc4fc554c7c6c7840ca4c6.jpg)
![¿Cómo recibir avisos sobre nuevos artículos de la RESP? [PARA LECTORES]](https://ojs.sanidad.gob.es/public/site/images/rmartinb/pastilla-lectores-aa689338e95aab07df45b4b0d583188f.jpg)
