Derek Wong1, Silvia Tortorelli2, Lisa Bishop3, Elizabeth A Sellars4, Lisa A Schimmenti5,6,7, Natalie Gallant1, Carlos E Prada8, Robert J Hopkin8, Nancy D Leslie8, Susan A Berry5,6,7, David S Rosenblatt9, Amy L Fair10, Dietrich Matern2, Kimiyo Raymond2, Devin Oglesbee2, Piero Rinaldo2, Dimitar Gavrilov2. 1. Department of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. 2. Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. 3. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. 4. Department of Pediatrics, Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 5. Department of Pediatrics, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA. 6. Department of Ophthalmology, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA. 7. Department of Genetics, Cell Biology and Development, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA. 8. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 9. Department of Human Genetics, McGill University and the Research Institute of the McGill University Health Center, Montreal, Quebec, Canada. 10. Fairview Elk River Clinic, Elk River, Minnesota, USA.
Abstract
PURPOSE: We evaluated the clinical outcome in homocysteine remethylation disorders following newborn screening (NBS) and initiation of early specific treatment. METHODS: Five patients with remethylation disorders were included in this study. RESULTS: Two asymptomatic patients (one with cblG and one with cblE) were identified by NBS using an approach that combines a postanalytical interpretive tool (available on the Region 4 Stork (R4S) collaborative project website, http://www.clir-r4s.org) and a second-tier test for total homocysteine determination. Both the initial screening and the second-tier test are performed on the same blood spot, with no additional patient contact, resulting in no false-positive outcomes. Two additional patients with methylenetetrahydrofolate reductase deficiency were detected by NBS using low methionine as a marker. Although already symptomatic despite the early diagnosis, the latter two patients greatly improved with treatment and their outcomes are compared with that of another patient with methylenetetrahydrofolate reductase deficiency and significant morbidity who was diagnosed clinically at 3 months of age. CONCLUSION: Early detection by NBS and timely and specific treatment considerably improve at least short-term outcomes of homocysteine remethylation disorders. When a remethylation disorder is suspected, group-specific treatment could be started prior to the completion of in vitro confirmatory testing because all disorders from this group require similar intervention.
PURPOSE: We evaluated the clinical outcome in homocysteine remethylation disorders following newborn screening (NBS) and initiation of early specific treatment. METHODS: Five patients with remethylation disorders were included in this study. RESULTS: Two asymptomatic patients (one with cblG and one with cblE) were identified by NBS using an approach that combines a postanalytical interpretive tool (available on the Region 4 Stork (R4S) collaborative project website, http://www.clir-r4s.org) and a second-tier test for total homocysteine determination. Both the initial screening and the second-tier test are performed on the same blood spot, with no additional patient contact, resulting in no false-positive outcomes. Two additional patients with methylenetetrahydrofolate reductase deficiency were detected by NBS using low methionine as a marker. Although already symptomatic despite the early diagnosis, the latter two patients greatly improved with treatment and their outcomes are compared with that of another patient with methylenetetrahydrofolate reductase deficiency and significant morbidity who was diagnosed clinically at 3 months of age. CONCLUSION: Early detection by NBS and timely and specific treatment considerably improve at least short-term outcomes of homocysteine remethylation disorders. When a remethylation disorder is suspected, group-specific treatment could be started prior to the completion of in vitro confirmatory testing because all disorders from this group require similar intervention.
Authors: Petra Zavadáková; Brian Fowler; Terttu Suormala; Zorka Novotna; Peter Mueller; Julia B Hennermann; Jirí Zeman; M Antonia Vilaseca; Laura Vilarinho; Sven Gutsche; Ekkehard Wilichowski; Gerd Horneff; Viktor Kozich Journal: Hum Mutat Date: 2005-03 Impact factor: 4.878
Authors: Silvia Tortorelli; Coleman T Turgeon; James S Lim; Steve Baumgart; Debra-Lynn Day-Salvatore; Jose Abdenur; Jonathan A Bernstein; Fred Lorey; Uta Lichter-Konecki; Devin Oglesbee; Kimiyo Raymond; Dietrich Matern; Lisa Schimmenti; Piero Rinaldo; Dimitar K Gavrilov Journal: J Pediatr Date: 2010-04-14 Impact factor: 4.406
Authors: Kevin A Strauss; D Holmes Morton; Erik G Puffenberger; Christine Hendrickson; Donna L Robinson; Conrad Wagner; Sally P Stabler; Robert H Allen; Grazyna Chwatko; Hieronim Jakubowski; Mihai D Niculescu; S Harvey Mudd Journal: Mol Genet Metab Date: 2007-04-03 Impact factor: 4.797
Authors: M Huemer; C Bürer; P Ješina; V Kožich; M A Landolt; T Suormala; B Fowler; P Augoustides-Savvopoulou; E Blair; K Brennerova; A Broomfield; L De Meirleir; G Gökcay; J Hennermann; P Jardine; J Koch; S Lorenzl; A S Lotz-Havla; J Noss; R Parini; H Peters; B Plecko; F J Ramos; A Schlune; K Tsiakas; M Zerjav Tansek; M R Baumgartner Journal: J Inherit Metab Dis Date: 2014-12-20 Impact factor: 4.982
Authors: Coleman T Turgeon; Mark J Magera; Carla D Cuthbert; Perry R Loken; Dimitar K Gavrilov; Silvia Tortorelli; Kimiyo M Raymond; Devin Oglesbee; Piero Rinaldo; Dietrich Matern Journal: Clin Chem Date: 2010-08-31 Impact factor: 8.327
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
Authors: Gwendolyn Gramer; Junmin Fang-Hoffmann; Patrik Feyh; Glynis Klinke; Peter Monostori; Jürgen G Okun; Georg F Hoffmann Journal: World J Pediatr Date: 2018-06-15 Impact factor: 2.764
Authors: Jürgen G Okun; Hongying Gan-Schreier; Tawfeq Ben-Omran; Kathrin V Schmidt; Junmin Fang-Hoffmann; Gwendolyn Gramer; Ghassan Abdoh; Noora Shahbeck; Hilal Al Rifai; Abdul Latif Al Khal; Gisela Haege; Chuan-Chi Chiang; David C Kasper; Bridget Wilcken; Peter Burgard; Georg F Hoffmann Journal: JIMD Rep Date: 2016-06-21
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