Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns

Background Alteration of vitamin B-12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B-12 d...

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Autores: Pajares S, Arranz JA, Ormazabal A, Del Toro M, García-Cazorla Á, Navarro-Sastre A, López RM, Meavilla SM, de Los Santos MM, García-Volpe C, de Aledo-Castillo JMG, Argudo A, Marín JL, Carnicer C, Artuch R, Tort F, Gort L, Fernández R, García-Villoria J, Ribes A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p19570
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19570
Access Level:acceso abierto
Palabra clave:Vitamin B-12 deficiency
Homocysteine
Methylmalonic acid
Methylcitric acid
Newborn screening
Second-tier test
Methylmalonic acidemia
Propionic acidemia
Homocystinuria
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spelling Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newbornsPajares SArranz JAOrmazabal ADel Toro MGarcía-Cazorla ÁNavarro-Sastre ALópez RMMeavilla SMde Los Santos MMGarcía-Volpe Cde Aledo-Castillo JMGArgudo AMarín JLCarnicer CArtuch RTort FGort LFernández RGarcía-Villoria JRibes AVitamin B-12 deficiencyHomocysteineMethylmalonic acidMethylcitric acidNewborn screeningSecond-tier testMethylmalonic acidemiaPropionic acidemiaHomocystinuriaBackground Alteration of vitamin B-12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B-12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B-12) related disorders, both genetic and acquired conditions. Methods A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated. Results During the period 2015-2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B-12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia. Conclusions When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B-12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.BMC2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19570Orphanet Journal of Rare DiseasesISSN: 17501172reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p195702026-05-27T12:37:41Z
dc.title.none.fl_str_mv Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
title Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
spellingShingle Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
Pajares S
Vitamin B-12 deficiency
Homocysteine
Methylmalonic acid
Methylcitric acid
Newborn screening
Second-tier test
Methylmalonic acidemia
Propionic acidemia
Homocystinuria
title_short Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
title_full Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
title_fullStr Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
title_full_unstemmed Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
title_sort Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
dc.creator.none.fl_str_mv Pajares S
Arranz JA
Ormazabal A
Del Toro M
García-Cazorla Á
Navarro-Sastre A
López RM
Meavilla SM
de Los Santos MM
García-Volpe C
de Aledo-Castillo JMG
Argudo A
Marín JL
Carnicer C
Artuch R
Tort F
Gort L
Fernández R
García-Villoria J
Ribes A
author Pajares S
author_facet Pajares S
Arranz JA
Ormazabal A
Del Toro M
García-Cazorla Á
Navarro-Sastre A
López RM
Meavilla SM
de Los Santos MM
García-Volpe C
de Aledo-Castillo JMG
Argudo A
Marín JL
Carnicer C
Artuch R
Tort F
Gort L
Fernández R
García-Villoria J
Ribes A
author_role author
author2 Arranz JA
Ormazabal A
Del Toro M
García-Cazorla Á
Navarro-Sastre A
López RM
Meavilla SM
de Los Santos MM
García-Volpe C
de Aledo-Castillo JMG
Argudo A
Marín JL
Carnicer C
Artuch R
Tort F
Gort L
Fernández R
García-Villoria J
Ribes A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Vitamin B-12 deficiency
Homocysteine
Methylmalonic acid
Methylcitric acid
Newborn screening
Second-tier test
Methylmalonic acidemia
Propionic acidemia
Homocystinuria
topic Vitamin B-12 deficiency
Homocysteine
Methylmalonic acid
Methylcitric acid
Newborn screening
Second-tier test
Methylmalonic acidemia
Propionic acidemia
Homocystinuria
description Background Alteration of vitamin B-12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B-12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B-12) related disorders, both genetic and acquired conditions. Methods A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated. Results During the period 2015-2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B-12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia. Conclusions When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B-12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19570
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19570
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv Orphanet Journal of Rare Diseases
ISSN: 17501172
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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