Four Years’ Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers

  • B. Merinero
  • P. Alcaide
  • E. Martín-Hernández
  • A. Morais
  • M. T. García-Silva
  • P. Quijada-Fraile
  • C. Pedrón-Giner
  • E. Dulin
  • R. Yahyaoui
  • J. M. Egea
  • A. Belanger-Quintana
  • J. Blasco-Alonso
  • M. L. Fernandez Ruano
  • B. Besga
  • I. Ferrer-López
  • F. Leal
  • M. Ugarte
  • P. Ruiz-Sala
  • B. Pérez
  • C. Pérez-Cerdá
Research Report
Part of the JIMD Reports book series (JIMD, volume 39)

Abstract

Identification of very long-chain acyl-CoA dehydrogenase deficiency is possible in the expanded newborn screening (NBS) due to the increase in tetradecenoylcarnitine (C14:1) and in the C14:1/C2, C14:1/C16, C14:1/C12:1 ratios detected in dried blood spots. Nevertheless, different confirmatory tests must be performed to confirm the final diagnosis. We have revised the NBS results and the results of the confirmatory tests (plasma acylcarnitine profiles, molecular findings, and lymphocytes VLCAD activity) for 36 cases detected in three Spanish NBS centers during 4 years, correlating these with the clinical outcome and treatment. Our aim was to distinguish unambiguously true cases from disease carriers in order to obtain useful diagnostic information for clinicians that can be applied in the follow-up of neonates identified by NBS.

Increases in C14:1 and of the different ratios, the presence of two pathogenic mutations, and deficient enzyme activity in lymphocytes (<12% of the intra-assay control) identified 12 true-positive cases. These cases were given nutritional therapy and all of them are asymptomatic, except one. Seventeen individuals were considered disease carriers based on the mild increase in plasma C14:1, in conjunction with the presence of only one mutation and/or intermediate residual activity (18–57%). In addition, seven cases were classified as false positives, with normal biochemical parameters and no mutations in the exonic region of ACADVL. All these carriers and the false positive cases remained asymptomatic. The combined evaluation of the acylcarnitine profiles, genetic results, and residual enzyme activities have proven useful to definitively classify individuals with suspected VLCAD deficiency into true-positive cases and carriers, and to decide which cases need treatment.

Keywords

ACADVL mutations Newborn screening Very long-chain acyl-CoA dehydrogenase deficiency VLCAD enzyme activity 

Notes

Acknowledgments

The authors would like to thank the families involved in this study for giving their consent. This work was funded by a grant from the Fundación Isabel Gemio. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • B. Merinero
    • 1
  • P. Alcaide
    • 1
  • E. Martín-Hernández
    • 2
  • A. Morais
    • 3
  • M. T. García-Silva
    • 2
  • P. Quijada-Fraile
    • 2
  • C. Pedrón-Giner
    • 4
  • E. Dulin
    • 5
  • R. Yahyaoui
    • 6
  • J. M. Egea
    • 7
  • A. Belanger-Quintana
    • 8
  • J. Blasco-Alonso
    • 9
  • M. L. Fernandez Ruano
    • 5
  • B. Besga
    • 5
  • I. Ferrer-López
    • 1
  • F. Leal
    • 1
  • M. Ugarte
    • 1
  • P. Ruiz-Sala
    • 1
  • B. Pérez
    • 1
  • C. Pérez-Cerdá
    • 1
  1. 1.Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSICUniversidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IdiPAZMadridSpain
  2. 2.Departamento de Pediatría, Unidad de Enfermedades Mitocondriales-Metabólicas HereditariasHospital Universitario Doce de Octubre, Universidad Complutense de Madrid, CIBERERMadridSpain
  3. 3.Unidad de Nutrición Infantil y Enfermedades MetabólicasHospital Universitario Infantil La PazMadridSpain
  4. 4.Sección de Gastroenterología y NutriciónHospital Infantil Universitario Niño JesúsMadridSpain
  5. 5.Laboratorio de Cribado NeonatalHospital General Universitario Gregorio MarañónMadridSpain
  6. 6.Laboratorio de MetabolopatíasHospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA)MálagaSpain
  7. 7.Centro de Bioquímica y Genética Clínica, Unidad de MetabolopatíasHospital General Universitario Virgen de la ArrixacaMurciaSpain
  8. 8.Unidad de Enfermedades Metabólicas, Servicio de PediatríaHospital Universitario Ramón y CajalMadridSpain
  9. 9.Sección de Gastroenterología y Nutrición PediátricaHospital Regional de MálagaMálagaSpain

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