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

  • Álvaro Martín-Rivada ORCID logo EMAIL logo , Ana Cambra Conejero , Elena Martín-Hernández , Ana Moráis López , Amaya Bélanger-Quintana , Elvira Cañedo Villarroya , Pilar Quijada-Fraile , Marcelo Bellusci , Silvia Chumillas Calzada , Ana Bergua Martínez , Sinziana Stanescu , Mercedes Martínez-Pardo Casanova , Pedro Ruíz-Sala , Magdalena Ugarte , Belén Pérez González and Consuelo Pedrón-Giner
Published/Copyright: September 19, 2022
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 10

Abstract

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.

Keywords: inborn error of metabolism; methymalonic acidemia; neonatal screening; propionic acidemia; tandem mass spectrometry; vitamin B12
Corresponding author: Álvaro Martín Rivada, Sección de Gastroenterología y Nutrición, Hospital Infantil Universitario Niño Jesús, Menéndez Pelayo, 65 28009, Madrid, Spain, E-mail:

  1. Research funding: None declared.

  2. Author contributions: Dr. C. Pedrón-Giner had the original idea and contributed to planning the research design, methods, and preparation of manuscript. Dr. Á. Martín-Rivada contributed to data acquisition, carrying out aspects of the methods and statistical analysis and writing the draft of the manuscript. All authors have been involved in drafting the article and have expressed their agreement to submission.

  3. Competing interest statement: The authors declare that there was no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2022-07-05
Accepted: 2022-08-13
Published Online: 2022-09-19
Published in Print: 2022-10-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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  1. Frontmatter
  2. Original Articles
  3. Newborn screening for propionic, methylmalonic acidemia and vitamin B12 deficiency. Analysis of 588,793 newborns
  4. Use of letrozole to augment height outcome in pubertal boys: a retrospective chart review
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  12. Short Communication
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  14. Case Reports
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  16. Three pediatric cases of symptomatic hyponatremia in Prader–Willi syndrome
  17. Identification of a novel mutation in FGFR1 gene in mother and daughter with Kallmann syndrome
  18. Exaggerated mini-puberty in a preterm girl: a case report and review of literature
  19. Diabetic ketoacidosis masquerading behind alkalemia an undiagnosed or missed variant of diabetic ketoacidosis
https://doi.org/10.1515/jpem-2022-0340
Keywords for this article
inborn error of metabolism; methymalonic acidemia; neonatal screening; propionic acidemia; tandem mass spectrometry; vitamin B12

Articles in the same Issue

  1. Frontmatter
  2. Original Articles
  3. Newborn screening for propionic, methylmalonic acidemia and vitamin B12 deficiency. Analysis of 588,793 newborns
  4. Use of letrozole to augment height outcome in pubertal boys: a retrospective chart review
  5. Study of the frequency and clinical features of maturity-onset diabetes in the young in the pediatric and adolescent diabetes population in Iran
  6. Iatrogenic hyperthyroidism in primary congenital hypothyroidism: prevalence and predictive factors
  7. Utility of head CT scan in treatment decisions for suspected cerebral edema in children with DKA
  8. Newborn screening and genetic variation of medium chain acyl-CoA dehydrogenase deficiency in the Chinese population
  9. Performance of glucagon stimulation test in diagnosing central adrenal insufficiency in children when utilising the Roche Elecsys® cortisol II assay: a pilot study
  10. Effects and dose-response relationship of exercise training on cardiometabolic risk factors in children with obesity
  11. Biochemical indicators of euthyroid sick syndrome in critically ill children
  12. Short Communication
  13. Parental marital relationship satisfaction predicts glycemic outcomes in children with type 1 diabetes
  14. Case Reports
  15. Late onset Bartter syndrome: Bartter syndrome type 2 presenting with isolated nephrocalcinosis and high parathyroid hormone levels mimicking primary hyperparathyroidism
  16. Three pediatric cases of symptomatic hyponatremia in Prader–Willi syndrome
  17. Identification of a novel mutation in FGFR1 gene in mother and daughter with Kallmann syndrome
  18. Exaggerated mini-puberty in a preterm girl: a case report and review of literature
  19. Diabetic ketoacidosis masquerading behind alkalemia an undiagnosed or missed variant of diabetic ketoacidosis
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