Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
Por:
Pajares S, Arranz JA, Ormazabal-Herrero A, Del Toro M, Garcia-Cazorla A, 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-Iriberri R, Tort F, Gort L, Fernández R, García-Villoria J and Ribes A
Publicada:
30 abr 2021
Ahead of Print:
30 abr 2021
Resumen:
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.
Filiaciones:
Pajares S:
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
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Arranz JA:
Unit of Metabolic Diseases, Hospital Vall D'Hebrón, Barcelona, Spain
Ormazabal-Herrero A:
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain
Del Toro M:
Unit of Metabolic Diseases, Hospital Vall D'Hebrón, Barcelona, Spain
Garcia-Cazorla A:
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain
Navarro-Sastre A:
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
López RM:
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
Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Meavilla SM:
Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain
de los Santos MM:
Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain
García-Volpe C:
Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain
de Aledo-Castillo JMG:
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
Argudo A:
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
Marín JL:
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
Carnicer C:
Unit of Metabolic Diseases, Hospital Vall D'Hebrón, Barcelona, Spain
Artuch-Iriberri R:
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain
Tort F:
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
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Gort L:
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
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Fernández R:
Maternal and Child Health Service, Public Health Agency of Catalonia, Health Department, Government of Catalonia, Barcelona, Spain
García-Villoria J:
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
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Ribes A:
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.
Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain.
Biomedical Research Institute, August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Green Submitted, gold
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