Jon Bernstein

Publication Details

  • Two-Tier Approach to the Newborn Screening of Methylenetetrahydrofolate Reductase Deficiency and Other Remethylation Disorders with Tandem Mass Spectrometry JOURNAL OF PEDIATRICS Tortorelli, S., Turgeon, C. T., Lim, J. S., Baumgart, S., Day-Salvatore, D., Abdenur, J., Bernstein, J. A., Lorey, F., Lichter-Konecki, U., Oglesbee, D., Raymond, K., Matem, D., Schimmenti, L., Rinaldo, P., Gavrilov, D. K. 2010; 157 (2): 271-275


    To validate a 2-tier approach for newborn screening (NBS) of remethylation defects.The original NBS dried blood spots of 5 patients with a proven diagnosis of a remethylation disorder and 1 patient with biochemical evidence of such disorder were analyzed retrospectively to determine disease ranges for methionine (Met; 4.7-8.1 micromol/L; 1 percentile of healthy population, 11.1 micromol/L), the methionine/phenylalanine ratio (Met/Phe; 0.09-0.16; 1 percentile of healthy population, 0.22), and total homocysteine (tHcy; 42-157 micromol/L; 99 percentile of normal population, 14.7 micromol/L). These preliminary disease ranges showed a sufficient degree of segregation from healthy population data, allowing the selection of cutoff values. A simple algorithm was then developed to reflex cases to a second-tier testing for tHcy, which has been applied prospectively for 14 months.A total of 86 333 NBS samples were tested between January 2007 and March 2008, and 233 of them (0.27%) met the criteria for second-tier testing of tHcy. All cases revealed concentrations of tHcy <15 micromol/L and were considered unaffected. No false-negative results have been reported with a state-wide system based on 2 combined metabolic clinics and laboratories that cover the entire Minnesota population and border areas of neighboring states.Pending more conclusive evidence from the prospective identification of additional true-positive cases, NBS for remethylation disorders appears to be feasible with existing methodologies, with only a marginal increase of the laboratory workload.

    View details for DOI 10.1016/j.jpeds.2010.02.027

    View details for Web of Science ID 000279871700023

    View details for PubMedID 20394947

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