The Journal of Pediatrics
Volume 157, Issue 2 , Pages 271-275 , August 2010

Two-Tier Approach to the Newborn Screening of Methylenetetrahydrofolate Reductase Deficiency and Other Remethylation Disorders with Tandem Mass Spectrometry

  • Silvia Tortorelli, MD, PhD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • Coleman T. Turgeon

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • James S. Lim, PhD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • Steve Baumgart, MD

      Affiliations

    • Children's National Medical Center, Washington, DC
    • ,
  • Debra-Lynn Day-Salvatore, MD, PhD

      Affiliations

    • Institute for Genetic Medicine, St. Peter's University Hospital, New Brunswick, NJ
    • ,
  • Jose Abdenur, MD

      Affiliations

    • CHOC Children's, Orange County, CA
    • ,
  • Jonathan A. Bernstein, MD, PhD

      Affiliations

    • Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA
    • ,
  • Fred Lorey, PhD

      Affiliations

    • California Department of Public Health, Richmond, CA
    • ,
  • Uta Lichter-Konecki, MD, PhD

      Affiliations

    • Children's National Medical Center, Washington, DC
    • ,
  • Devin Oglesbee, PhD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • Kimiyo Raymond, MD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • Dietrich Matern, MD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • Lisa Schimmenti, MD

      Affiliations

    • Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
    • ,
  • Piero Rinaldo, MD, PhD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • ,
  • Dimitar K. Gavrilov, MD, PhD

      Affiliations

    • Department of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, MN
    • Corresponding Author InformationReprint requests: Dimitar Gavrilov, MD, PhD, Biochemical Genetics Laboratory - Hilton 330, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.

Received 21 August 2009 ,Revised 20 January 2010 ,Accepted 17 February 2010.

References 

  1. Ogier de Baulny H, Gerard M, Saudubray JM, Zittoun J. Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr. 1998;157(Suppl. 2):S77–S83
  2. Strauss KA, Morton DH, Puffenberger EG, Hendrickson C, Robinson DL, Wagner C, et al. Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency. Mol Genet Metab. 2007;91:165–175
  3. Watson M, Lloyd-Puryear M, Rinaldo P, Howell R, editors. Newborn screening: toward a uniform screening panel and system. Executive summary. Genet Med 2006; 8 (Suppl):1–11S.
  4. Matern D, Tortorelli S, Oglesbee D, Gavrilov D, Rinaldo P. Reduction of the false-positive rate in newborn screening by implementation of MS/MS-based second-tier tests: the Mayo Clinic experience (2004-2007). J Inherit Metab Dis. 2007;30:585–592
  5. Miousse IR, Watkins D, Coelho D, Rupar T, Crombez EA, Vilain E, et al. Clinical and molecular heterogeneity in patients with the cblD inborn error of cobalamin metabolism. J Pediatr. 2009;154:551–556
  6. Turgeon C, Magera MJ, Allard P, Tortorelli S, Gavrilov D, Oglesbee D, et al. Combined newborn screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem. 2008;54:657–664
  7. Matern D CC, Magera MJ, Tortorelli S, Hahn S, Rinaldo P. A reporting algorithm for elevated propionylcarnitine (C3) including a 2nd tier test for methylmalonic acid and homocysteine. Paper presented at 2005 Newborn Screening and Genetic Testing Symposium. Portland, OR; 2005.
  8. Suormala T, Baumgartner MR, Coelho D, Zavadakova P, Kozich V, Koch HG, et al. The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis. J Biol Chem. 2004;279:42742–42749
  9. Rosenblatt D. Inherited disorders of folate and cobalamin transport and metabolism. In:  Scriver CR,  Sly WS,  Valle D editor. Metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001;p. 24–31
  10. Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol. 1999;36:19–34
  11. Al Tawari AA, Ramadan DG, Neubauer D, Heberle LC, Al Awadi F. An early onset form of methylenetetrahydrofolate reductase deficiency: a report of a family from Kuwait. Brain Dev. 2002;24:304–309
  12. Abeling NG, van Gennip AH, Blom H, Wevers RA, Vreken P, van Tinteren HL, et al. Rapid diagnosis and methionine administration: basis for a favourable outcome in a patient with methylene tetrahydrofolate reductase deficiency. J Inherit Metab Dis. 1999;22:240–242
  13. Walk D, Kang SS, Horwitz A. Intermittent encephalopathy, reversible nerve conduction slowing, and MRI evidence of cerebral white matter disease in methylenetetrahydrofolate reductase deficiency. Neurology. 1994;44:344–347
  14. Fattal-Valevski A, Bassan H, Korman SH, Lerman-Sagie T, Gutman A, Harel S. Methylenetetrahydrofolate reductase deficiency: importance of early diagnosis. J Child Neurol. 2000;15:539–543
  15. Ucar SK, Koroglu OA, Berk O, Yalaz M, Kultursay N, Blom HJ, et al. Titration of betaine therapy to optimize therapy in an infant with 5,10-methylenetetrahydrofolate reductase deficiency. Eur J Pediatr. 2010;169
  16. Cooper BA, Rosenblatt DS. Inherited defects of vitamin B12 metabolism. Annu Rev Nutr. 1987;7:291–320
  17. Watkins D, Rosenblatt DS. Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. Am J Med Genet. 1989;34:427–434
  18. Hall CA. Function of vitamin B12 in the central nervous system as revealed by congenital defects. Am J Hematol. 1990;34:121–127
  19. Hall CA, Lindenbaum RH, Arenson E, Begley JA, Chu RC. The nature of the defect in cobalamin G mutation. Clin Invest Med. 1989;12:262–269
  20. Rosenblatt DS, Thomas IT, Watkins D, Cooper BA, Erbe RW. Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency. Am J Med Genet. 1987;26:377–383
  21. Strnadova KA, Holub M, Muhl A, Heinze G, Ratschmann R, Mascher H, et al. Long-term stability of amino acids and acylcarnitines in dried blood spots. Clin Chem. 2007;53:717–722
  22. Therrell BL, Hannon WH, Pass KA, Lorey F, Brokopp C, Eckman J, et al. Guidelines for the retention, storage, and use of residual dried blood spot samples after newborn screening analysis: statement of the Council of Regional Networks for Genetic Services. Biochem Mol Med. 1996;57:116–124
  23. Chace DH, Adam BW, Smith SJ, Alexander JR, Hillman SL, Hannon WH. Validation of accuracy-based amino acid reference materials in dried-blood spots by tandem mass spectrometry for newborn screening assays. Clin Chem. 1999;45:1269–1277

 The authors declare no conflicts of interest.

PII: S0022-3476(10)00151-4

doi: 10.1016/j.jpeds.2010.02.027

The Journal of Pediatrics
Volume 157, Issue 2 , Pages 271-275 , August 2010

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