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

Orphanet Journal of Rare Diseases

Rafael Artuch¹  Ángeles García-Cazorla¹  Aida Ormazabal¹  Silvia María Meavilla²  Camila García-Volpe²  Mariela Mercedes de los Santos²  Rosa Fernández³  Jose Manuel González de Aledo-Castillo⁴  Jose Luís Marín⁴  Aleix Navarro-Sastre⁴  Ana Argudo⁴  Rosa María López⁵  Sonia Pajares⁶  Frederic Tort⁷  Antonia Ribes⁷  Laura Gort⁷  Judit García-Villoria⁷  Clara Carnicer⁸  Mireia Del Toro⁸  Jose Antonio Arranz⁸ 

[1]Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain

[2]Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain

[3]Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain

[4]Maternal and Child Health Service, Public Health Agency of Catalonia, Health Department, Government of Catalonia, Barcelona, Spain

[5]Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica Y Genética Molecular, Hospital Clínic de Barcelona, C/ Mejía Lequerica S/N, Edificio Helios III, 08028, Barcelona, Spain

[6]Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica Y Genética Molecular, Hospital Clínic de Barcelona, C/ Mejía Lequerica S/N, Edificio Helios III, 08028, Barcelona, Spain

[7]Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain

[8]Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica Y Genética Molecular, Hospital Clínic de Barcelona, C/ Mejía Lequerica S/N, Edificio Helios III, 08028, Barcelona, Spain

[9]Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain

[10]Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica Y Genética Molecular, Hospital Clínic de Barcelona, C/ Mejía Lequerica S/N, Edificio Helios III, 08028, Barcelona, Spain

[11]Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain

[12]Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain

[13]Unit of Metabolic Diseases, Hospital Vall D’Hebrón, Barcelona, Spain

关键词: Vitamin B deficiency;    Homocysteine;    Methylmalonic acid;    Methylcitric acid;    Newborn screening;    Second-tier test;    Methylmalonic acidemia;    Propionic acidemia;    Homocystinuria;   

DOI  :  10.1186/s13023-021-01784-7

来源: Springer

【 摘 要 】

BackgroundAlteration of vitamin B12 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 B12 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 B12) related disorders, both genetic and acquired conditions.MethodsA 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.ResultsDuring the period 2015–2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 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.ConclusionsWhen screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 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.

【 授权许可】

CC BY