Newborn Screening and High Risk Screening Population for Neurological Inherited Metabolic Diseases

  • Alberto BurlinaEmail author
  • Giulia Polo


Nowadays, it is possible to carry on screening tests for many of the inherited metabolic disorders currently recognized. Laboratory investigations are complex and susceptible to technical problems. Since 1970s, batteries of relatively inexpensive tests named screening for metabolic diseases that can be carried out rapidly on a large numbers of specimens have been developed.

Metabolic screening is different according to the age of patients. In the neonatal period, this approach represents an example of epidemiological/medical intervention, which allows to identify neonates affected by a specific disease before the development of clinical signs of the condition, with the objective of initiating a treatment that would prevent serious disability or even death. Nowdays, expanded newborn screening based on tandem mass spectrometry technique allows the identification more than 60 diseases. This technique identifies defects of amino acids, organic acids, urea cycle, fatty acid oxidation metabolism, lysosomal diseases and peroxisomal diseases.

Subsequently, high risk population screening can be performed in order to identify the disease (diagnosis) even the specific therapeutical intervention might not be expected to alter the natural history of the disease. However, the process is initiated by the patient presenting symptoms. This approach has been proposed for mitochondrial and lysosomal diseases and neurodegenerative disorders.


Inherited metabolic diseases Expanded neonatal screening Selective screening Aminoacid disorders Organic acidurias Urea cycle defects Lysosomal disorders Fatty acid defects Stroke Neurodegenerative disorders 


  1. 1.
    Saudubray JM, Baumgartner MR, Walter J. Inborn metabolic diseases, diagnosis and treatment. 6th ed. New York: Springer; 2016.CrossRefGoogle Scholar
  2. 2.
    Vernon HJ. Inborn errors of metabolism: advances in diagnosis and therapy. JAMA Pediatr. 2015;169(8):778–82.CrossRefPubMedGoogle Scholar
  3. 3.
    Hoffmann GF, Zschocke J, Nyhan WL. Inherited metabolic diseases, a clinical approach. 2nd ed. New York: Springer; 2016.Google Scholar
  4. 4.
    Hollak C, Lachmann R, editors. Inherited metabolic disease in adults, a clinical guide. Oxford: Oxford University Press; 2016.Google Scholar
  5. 5.
    Garcia-Cazorla A, Wolf NI, Serrano M, et al. Mental retardation and inborn errors of metabolism. I Inherit Metab Dis. 2009;32:597–608.CrossRefGoogle Scholar
  6. 6.
    Sedel F, Baumann N, Turpin JC, Lyon-Caen O, Saudubray JM, Cohen D. Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults. J Inherit Metab Dis. 2007;30(5):631–41.CrossRefPubMedGoogle Scholar
  7. 7.
    McCormick E, Place E, Falk MJ. Molecular genetic testing for mitochondrial disease: from one generation to the next. Neurotherapeutics. 2013;10(2):251–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Wong LJ. Next generation molecular diagnosis of mitochondrial disorders. Mitochondrion. 2013;13(4):379–87.CrossRefPubMedGoogle Scholar
  9. 9.
    Matern D, Greene CL. Newborn screening. In: Blau N, Duran M, Gibson KM, Vici CD, Blaskovics M, editors. Physician’s guide to the diagnosis, treatment, and follow-up of metabolic diseases. New York: Springer; 2014.Google Scholar
  10. 10.
    Watson MS, Lloyd-Puryear MA, Mann MY, Rinaldo P, Howell RR. Newborn screening: toward a uniform screening panel and system. Genet Med. 2006;8(5S):12S–252S.CrossRefGoogle Scholar
  11. 11.
    Spiekerkoetter U. Mitochondrial fatty acid oxidation disorders: clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening. J Inherit Metab Dis. 2010;33(5):527–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Wilcken B, Haas M, Joy P, et al. Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet. 2007;369(9555):37–42.CrossRefPubMedGoogle Scholar
  13. 13.
    Lindner M, Hoffmann GF, Matern D. Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting. J Inherit Metab Dis. 2010;33(5):521–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Matern D, Gavrilov D, Oglesbee D, Raymond K, Rinaldo P, et al. Newborn screening for lysosomal storage disorders. Semin Perinatol. 2015;39(3):206–16.CrossRefPubMedGoogle Scholar
  15. 15.
    Gelb MH, Scott CR, Turecek F. Newborn screening for lysosomal storage diseases. Clin Chem. 2015;61(2):335–46.CrossRefPubMedGoogle Scholar
  16. 16.
    Burlina AB, Polo G, Salviati L, et al. Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy. J Inherit Metab Dis. 2018;41(2):209–19.CrossRefPubMedGoogle Scholar
  17. 17.
    Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H, Ponzone A, Desnick RJ. High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet. 2006;79(1):31–40.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, Yeh HY, Chao MC, Lin SJ, Kitagawa T, Desnick RJ, Hsu LW. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A). Hum Mutat. 2009;30(10):1397–405.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lisi EC, McCandless SE. Newborn screening for Lysosomal storage disorders: views of genetic healthcare providers. J Genet Couns. 2016;25(2):373–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Garcia-Cazorla A, Wolf N, Serrano M, et al. Inborn errors of metabolism and motor disturbances in children. J Inherit Metab Dis. 2009;32:618–29.CrossRefPubMedGoogle Scholar
  21. 21.
    Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 1: Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Arch Neurol. 2010;67(1):19–24.CrossRefPubMedGoogle Scholar
  22. 22.
    Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol. 2010;67(2):148–53.CrossRefPubMedGoogle Scholar
  23. 23.
    Vanier MT, Gissen P, Bauer P, Coll MJ, Burlina A, Hendriksz CJ, Latour P, Goizet C, Welford RW, Marquardt T, Kolb SA. Diagnostic tests for Niemann-Pick disease type C (NP-C): a critical review. Mol Genet Metab. 2016;118(4):244–54.CrossRefGoogle Scholar
  24. 24.
    Olpin SE, Murphy E, Kirk RJ, Taylor RW, Quinlivan R. The investigation and management of metabolic myopathies. J Clin Pathol. 2015;68(6):410–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Parikh S, Bernard G, Leventer RJ, van der Knaap MS, van Hove J, Pizzino A, McNeill NH, Helman G, Simons C, Schmidt JL, Rizzo WB, Patterson MC, Taft RJ, Vanderver A, GLIA Consortium. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Mol Genet Metab. 2015;114(4):501–15.CrossRefPubMedGoogle Scholar
  26. 26.
    Polo G, Burlina AP, Kolamunnage TB, Zampieri M, Dionisi-Vici C, Strisciuglio P, Zaninotto M, Plebani M, Burlina AB. Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS. Clin Chem Lab Med. 2017;55(3):403–14.CrossRefGoogle Scholar
  27. 27.
    Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R, Anselm I, Cohen BH, Falk MJ, Greene C, Gropman AL, Haas R, Hirano M, Morgan P, Sims K, Tarnopolsky M, Van Hove JL, Wolfe L, DiMauro S. Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2015;17(9):689–701.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, Department of Woman’s and Child’s HealthUniversity HospitalPadovaItaly

Personalised recommendations