Newborn Screening for Lysosomal Storage Disorders

  • C. Ronald Scott
  • Frantisek Turecek
  • Michael H. Gelb

Screening newborn infants for treatable metabolic diseases has been in existence for over four decades. It was initiated by Dr. Robert McCready in 1962 in the Massachusetts Department of Public Health and was based on the work of Dr. Robert Guthrie for the detection of phenylketonuria. The initiation of screening for phenylketonuria and its subsequent expansion to include congenital hypothyroidism, galactosemia, congenital adrenal hyperplasia, biotinidase deficiency, and hemoglobin abnormalities has had a profound effect in preventing the serious consequences from these disorders in susceptible individuals (for review, see Levy and Albers, 2000). The basis of newborn screening is founded on the availability of a simple test that can be performed on a drop of blood obtained from an infant. In practice, several drops of blood are obtained from the infant near the time of birth, placed on specific filter papers, and submitted to the laboratory for analysis. Thus, the simple availability of a blood spot is both the power and limitation behind newborn screening. The limitation is devising techniques for the detection of some disorders that may more easily be detected by using a different biologic specimen. Wilson and Junger (1968) outlined the principles that needed to be met to have a successful candidate for newborn screening. This was prepared as a statement of the World Health Organization (WHO).


Enzyme Replacement Therapy Fabry Disease Congenital Adrenal Hyperplasia Newborn Screening Gauche Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. An, Y., Young, S.P., Hillman, S.L., Van Hove, J.L., Chen, Y.T., and Millington, D.S., 2000, Liquid chromatographic assay for a glucose tetrasaccharide, a putative bio-marker for the diagnosis of Pompe disease, Anal Biochem. 287:136.CrossRefPubMedGoogle Scholar
  2. Barton, N.W., Brady, R.O., Dambrosia, J.M., Di Bisceglie, A.M., Doppelt, S.H., Hill, S.C., Mankin, H.J., Murray, G.J., Parker, R.I., Argoff, C.E., et al., 1991, Replacement therapy for inherited enzyme deficiency—Macrophage-targeted glucocerebrosidase for Gaucher’s disease, N Engl J Med. 324:1464.PubMedCrossRefGoogle Scholar
  3. Chamoles, N.A., Blanco, M.B., Gaggioli, D., and Casentini, C., 2001, Hurler-like pheno-type: Enzymatic diagnosis in dried blood spots on filter paper, Clin Chem. 47:2098.PubMedGoogle Scholar
  4. Chamoles, N.A., Blanco, M., Gaggioli, D., and Casentini, C., 2002a, Gaucher and Niemann-Pick diseases—Enzymatic diagnosis in dried blood spots on filter paper: Retrospective diagnoses in newborn-screening cards, Clin Chim Acta. 317:191.CrossRefGoogle Scholar
  5. Chamoles, N.A., Blanco, M., Gaggioli, D., and Casentini, C., 2002b, Tay-Sachs and Sandhoff diseases: Enzymatic diagnosis in dried blood spots on filter paper: Retro-spective diagnoses in newborn-screening cards, Clin Chim Acta. 318:133.CrossRefGoogle Scholar
  6. Chamoles, N.A., Niizawa, G., Blanco, M., Gaggioli, D., and Casentini, C., 2004, Glycogen storage disease type II: Enzymatic screening in dried blood spots on filter paper, Clin Chim Acta. 347:97.CrossRefPubMedGoogle Scholar
  7. Eng, C.M., Guffon, N., Wilcox, W.R., Germain, D.P., Lee, P., Waldek, S., Caplan, L., Linthorst, G.E., and Desnick, R.J., 2001, Safety and efficacy of recombinant human alpha-galactosidase A—Replacement therapy in Fabry’s disease, N Engl J Med. 345:9.CrossRefPubMedGoogle Scholar
  8. Gerber, S.A., Scott, C.R., Turecek, F., and Gelb, M.H., 2001, Direct profiling of multiple enzyme activities in human cell lysates by affinity chromatography/electrospray ioni-zation mass spectrometry: Application to clinical enzymology, Anal Chem. 73:1651.CrossRefPubMedGoogle Scholar
  9. Hua, C.T., Hopwood, J.J., Carlsson, S.R., Harris, R.J., and Meikle, P.J., 1998, Evaluation of the lysosome-associated membrane protein LAMP-2 as a marker for lysosomal storage disorders, Clin Chem. 44:2094.PubMedGoogle Scholar
  10. Krivit, W., Peters, C., and Shapiro, E.G., 1999, Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachro-matic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartyl-glucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III, 1999, Curr Opinion Neurol. 12:167.CrossRefGoogle Scholar
  11. Levy, H.L., and Albers, S., 2000, Genetic screening of newborns, Annu Rev Genomics Hum Genet. 1:139.CrossRefPubMedGoogle Scholar
  12. Li, Y., Scott, C.R., Chamoles, N.A., Ghavami, A., Pinto, B.M., Turecek, F., and Gelb, .H., 2004, Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening, Clin Chem. doi:10.1373/clinchem.2004.035907.Google Scholar
  13. Meikle, P.J., and Hopwood, J.J., 2003, Lysosomal storage disorders: Emerging therapeutic options require early diagnosis, Eur J Pediatr. 162 Suppl 1:S34.CrossRefPubMedGoogle Scholar
  14. Meikle, P.J., Brooks, D.A., Ravenscroft, E.M., Yan, M., Williams, R.E., Jaunzems, A.E., Chataway, T.K., Karageorgos, L.E., Davey, R.C., Boulter, C.D., Carlsson, S.R., and Hopwood, J.J., 1997, Diagnosis of lysosomal storage disorders: Evaluation of lyso-some-associated membrane protein LAMP-1 as a diagnostic marker, Clin Chem. 43:1325.PubMedGoogle Scholar
  15. Rozaklis, T., Ramsay, S.L., Whitfield, P.D., Ranieri, E., Hopwood, J.J., and Meikle, P.J., 2002, Determination of oligosaccharides in Pompe disease by electrospray ionization tandem mass spectrometry, Clin Chem. 48:131.PubMedGoogle Scholar
  16. Umapathysivam, K., Hopwood, J.J., and Meikle, P.J., 2001, Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease, Clin Chem. 47:1378.PubMedGoogle Scholar
  17. Umapathysivam, K., Whittle, A.M., Ranieri, E., Bindloss, C., Ravenscroft, E.M., van Diggelen, O.P., Hopwood, J.J., and Meikle, P.J., 2000, Determination of acid alpha-glucosidase protein: Evaluation as a screening marker for Pompe disease and other lysosomal storage disorders, Clin Chem. 46:1318.PubMedGoogle Scholar
  18. Wilcken, B., Wiley, V., Hammond, J., and Carpenter, K., 2003, Screening newborns for inborn errors of metabolism by tandem mass spectrometry, N Engl J Med. 348:2304.CrossRefPubMedGoogle Scholar
  19. Wilcox, W.R., Banikazemi, M., Guffon, N., Waldek, S., Lee, P., Linthorst, G.E., Desnick, R.J., and Germain, D.P., 2004, Long-term safety and efficacy of enzyme replacement therapy for Fabry disease, Am J Hum Genet. 75:65.CrossRefPubMedGoogle Scholar
  20. Wilson, J., and Junger, G., 1968, The Principles and Practice of Screening for Disease, World Health Organization, Geneva.Google Scholar
  21. Young, S.P., Stevens, R.D., An, Y., Chen, Y.T., and Millington, D.S., 2003, Analysis of a glucose tetrasaccharide elevated in Pompe disease by stable isotope dilution-electrospray ionization tandem mass spectrometry, Anal Biochem. 316:175.CrossRefPubMedGoogle Scholar
  22. Zytkovicz, T.H., Fitzgerald, E.F., Marsden, D., et al., 2001, Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: A two-year summary from the New England Newborn Screening Program, Clin Chem. 47:1945.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • C. Ronald Scott
    • 1
  • Frantisek Turecek
    • 2
  • Michael H. Gelb
    • 3
  1. 1.Department of PediatricsUniversity of WashingtonSeattleUSA
  2. 2.Department of ChemistryUniversity of WashingtonSeattleUSA
  3. 3.Department of BiochemistryUniversity of WashingtonSeattleUSA

Personalised recommendations