OBJECTIVE: To validate a 2-tier approach for newborn screening (NBS) of remethylation defects. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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. Copyright (c) 2010 Mosby, Inc. All rights reserved.
OBJECTIVE: To validate a 2-tier approach for newborn screening (NBS) of remethylation defects. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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. Copyright (c) 2010 Mosby, Inc. All rights reserved.
Authors: Ana Marcão; María L Couce; Célia Nogueira; Helena Fonseca; Filipa Ferreira; José M Fraga; M Dolores Bóveda; Laura Vilarinho Journal: JIMD Rep Date: 2015-02-01
Authors: Derek Wong; Silvia Tortorelli; Lisa Bishop; Elizabeth A Sellars; Lisa A Schimmenti; Natalie Gallant; Carlos E Prada; Robert J Hopkin; Nancy D Leslie; Susan A Berry; David S Rosenblatt; Amy L Fair; Dietrich Matern; Kimiyo Raymond; Devin Oglesbee; Piero Rinaldo; Dimitar Gavrilov Journal: Genet Med Date: 2015-04-09 Impact factor: 8.822
Authors: Martina Huemer; Daria Diodato; Bernd Schwahn; Manuel Schiff; Anabela Bandeira; Jean-Francois Benoist; Alberto Burlina; Roberto Cerone; Maria L Couce; Angeles Garcia-Cazorla; Giancarlo la Marca; Elisabetta Pasquini; Laura Vilarinho; James D Weisfeld-Adams; Viktor Kožich; Henk Blom; Matthias R Baumgartner; Carlo Dionisi-Vici Journal: J Inherit Metab Dis Date: 2016-11-30 Impact factor: 4.982
Authors: Patricia L Hall; Gregg Marquardt; David M S McHugh; Robert J Currier; Hao Tang; Stephanie D Stoway; Piero Rinaldo Journal: Genet Med Date: 2014-05-29 Impact factor: 8.822