Newborn screening for propionic, methylmalonic acidemia and vitamin B12 deficiency. Analysis of 588,793 newborns.

OBJECTIVES: We present the results of our experience in the diagnosis and follow up of the positive cases for propionic, methylmalonic acidemias and cobalamin deficiencies (PA/MMA/MMAHC) since the Expanded Newborn Screening was implemented in Madrid Region. METHODS: Dried blood samples were collected 48 h after birth. Amino acids and acylcarnitines were quantitated by MS/MS. Newborns with alterations were referred to the clinical centers for follow-up. Biochemical and molecular genetic studies for confirmation of a disease were performed. RESULTS: In the period 2011-2020, 588,793 children were screened, being 953 of them were referred to clinical units for abnormal result (192 for elevated C3 levels). Among them, 88 were false positive cases, 85 maternal vitamin B12 deficiencies and 19 were confirmed to suffer an IEM (8 PA, 4 MMA, 7 MMAHC). Ten out 19 cases displayed symptoms before the NBS results (6 PA, 1 MMA, 3 MMAHC). C3, C16:1OH+C17 levels and C3/C2 and C3/Met ratios were higher in newborns with PA/MMA/MMAHC. Cases diagnosed with B12 deficiency had mean B12 levels of 187.6 ± 76.9 pg/mL and their mothers 213.7 ± 95.0; 5% of the mothers were vegetarian or had poor eating while 15% were diagnosed of pernicious anemia. Newborns and their mothers received treatment with B12 with different posology, normalizing their levels and the secondary alterations disappeared. CONCLUSIONS: Elevated C3 are a frequent cause for abnormal result in newborn screening with a high rate of false positive cases. Presymptomatic diagnosis of most of PA and some MMA/MMAHC is difficult. Vitamin B12 deficiency secondary to maternal deprivation is frequent with an heterogenous clinical and biochemical spectrum.

[Newborn Screening Program in the Community of Madrid: evaluation of positive cases.] / Análisis de casos positivos de cribado neonatal de errores congénitos del metabolismo en la Comunidad de Madrid.

OBJECTIVE: 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.

OBJETIVO: La tecnología de espectrometría de masas en tándem (MS/MS) en los programas de cribado neonatal ha permitido la detección de gran número de errores congénitos del metabolismo (ECM). En la comunidad de Madrid se implementó en marzo de 2011 incluyendo 13 aminoacidopatías, defectos de la ß-oxidación de ácidos grasos y acidemias orgánicas. El objetivo de este estudio fue describir nuestra experiencia y analizar los casos positivos de cribado en un periodo de 9 años (2011-2019). METODOS: Durante el periodo de estudio se realizó el cribado mediante MS/MS a 592822 recién nacidos en la Comunidad de Madrid. Se cuantificaron aminoácidos, acilcarnitinas y succinilacetona en todas las muestras que cumplieron los criterios de calidad. Se calcularon medias, medianas, percentiles y desviación típica de los analitos y ratios de interés. RESULTADOS: Se derivaron a las unidades clínicas de seguimiento por sospecha de una ECM un total de 901 (0,15 %) casos. Se confirmaron 230 casos de 30 ECM diferentes (prevalencia 1:2577), 11 de los cuales no eran inicialmente objetivo de detección del programa. El valor predictivo positivo global fue de 25,6 %. Durante este periodo se detectaron dos falsos negativos. Las enfermedades con mayor prevalencia fueron fenilcetonuria/hiperfenilalaninemia y deficiencia de acil-CoA deshidrogenasa de cadena media (1:6444 y 1: 13174 respectivamente). 93 % de los casos fueron detectados en fase presintomática. CONCLUSIONES: En estos 9 años de experiencia se han detectado numerosos casos de ECM con un valor predictivo positivo global aceptable. Estos resultados confirman la utilidad del cribado neonatal de ECM como programa de salud pública.

Epilepsia dependiente de piridoxina por deficiencia en el gen PNPO / Pyridoxine-dependent epilepsy due to deficiency in the PNPO gene

No disponible

Afectación hepática de paciente portadora en heterocigosis de una mutación en el gen PHKA / Hepatic involvement in a female carrier heterozygous for a mutation in the PHKA2 gene

No disponible

Análisis de casos positivos de cribado neonatal de errores congénitos del metabolismo en la Comunidad de Madrid / Newborn Screening Program in the Community of Madrid: evaluation of positive cases

OBJETIVO: La tecnología de espectrometría de masas en tándem (MS/MS) en los programas de cribado neonatal ha permitido la detección de gran número de errores congénitos del metabolismo (ECM). En la comunidad de Madrid se implementó en marzo de 2011 incluyendo 13 aminoacidopatías, defectos de la beta-oxidación de ácidos grasos y acidemias orgánicas. El objetivo de este estudio fue describir nuestra experiencia y analizar los casos positivos de cribado en un periodo de 9 años (2011-2019). MÉTODOS: Durante el periodo de estudio se realizó el cribado mediante MS/MS a 592822 recién nacidos en la Comunidad de Madrid. Se cuantificaron aminoácidos, acilcarnitinas y succinilacetona en todas las muestras que cumplieron los criterios de calidad. Se calcularon medias, medianas, percentiles y desviación típica de los analitos y ratios de interés. RESULTADOS: Se derivaron a las unidades clínicas de seguimiento por sospecha de una ECM un total de 901 (0,15 %) casos. Se confirmaron 230 casos de 30 ECM diferentes (prevalencia 1:2577), 11 de los cuales no eran inicialmente objetivo de detección del programa. El valor predictivo positivo global fue de 25,6 %. Durante este periodo se detectaron dos falsos negativos. Las enfermedades con mayor prevalencia fueron fenilcetonuria/hiperfenilalaninemia y deficiencia de acil-CoA deshidrogenasa de cadena media (1:6444 y 1: 13174 respectivamente). 93 % de los casos fueron detectados en fase presintomática. CONCLUSIONES: En estos 9 años de experiencia se han detectado numerosos casos de ECM con un valor predictivo positivo global aceptable. Estos resultados confirman la utilidad del cribado neonatal de ECM como programa de salud pública

OBJECTIVE: 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