JIMD Reports (Mar 2022)

Diagnosis of inborn errors of metabolism within the expanded newborn screening in the Madrid region

  • Álvaro Martín‐Rivada,
  • Laura Palomino Pérez,
  • Pedro Ruiz‐Sala,
  • Rosa Navarrete,
  • Ana Cambra Conejero,
  • Pilar Quijada Fraile,
  • Ana Moráis López,
  • Amaya Belanger‐Quintana,
  • Elena Martín‐Hernández,
  • Marcello Bellusci,
  • Elvira Cañedo Villaroya,
  • Silvia Chumillas Calzada,
  • María Teresa García Silva,
  • Ana Bergua Martínez,
  • Sinziana Stanescu,
  • Mercedes Martínez‐Pardo Casanova,
  • Miguel L. F. Ruano,
  • Magdalena Ugarte,
  • Belén Pérez,
  • Consuelo Pedrón‐Giner

DOI
https://doi.org/10.1002/jmd2.12265
Journal volume & issue
Vol. 63, no. 2
pp. 146 – 161

Abstract

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Abstract We present the results of our experience in the diagnosis of inborn errors of metabolism (IEM) since the Expanded Newborn Screening was implemented in our Region. Dried blood samples were collected 48 h after birth. Amino acids and acylcarnitines were quantitated by mass spectrometry (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. In the period 2011 to 2019, 592 822 children were screened: 902 of them were referred for abnormal results. An IEM was confirmed in 222 (1/2670): aminoacidopathies: 89 hyperphenylalaninemia (HPA) (51 benign HPA, 32 phenylketonuria, 4 DNAJC12 defect, and 2 primapterinuria), 6 hypermethioninemia, 3 tyrosinemia type 1 (TYR‐1), 1 TYR‐3, 4 maple syrup urine disease (MSUD), 2 branched‐chain amino acid transferase 2 deficiency, 2 homocystinuria, 1 cystinuria, 2 ornithine transcarbamylase (OTC) deficiency, 2 citrullinemia type I (CTLN1); FAO defects: 43 medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD), 13 very long‐chain acyl‐CoA dehydrogenase deficiency, 2 long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency (LCHADD), 1 multiple acyl‐coA dehydrogenation deficiency, 11 systemic primary carnitine deficiency, 2 carnitine palmitoyltransferase type 2 (CPT‐II) deficiency, 1 CPT‐I deficiency; organic acidurias: 12 glutaric aciduria type 1 (GA‐1), 4 methylmalonic acidemia (MMA), 7 MMA including combined cases with homocystinuria (MMAHC), 6 propionic acidemia (PA), 7 3‐methylcrotonyl‐CoA carboxylase, 1 3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency lyase deficiency. Only 19 infants (8.5%) were symptomatic at newborn screening result (1 LCHADD, 5 PA, 1 CPT‐II deficiency, 1 MMA, 3 MMAHC, 2 MSUD, 2 OTC deficiency, 1 CTLN1, 1 MCADD, 2 TYR‐1). No false negative cases were identified. Genetic diagnosis was conclusive in all biochemically confirmed cases, except for two infants with HPA, identifying pathogenic variants in 32 different genes. The conditions with the highest incidence were HPA (1/6661) and MCAD deficiencies (1/13 787).

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