title: Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors: Derek
authors: http://orcid.org/0000-0002-7762-2276
authors: D
authors: Wong
authors: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Silvia
authors: S
authors: Tortorelli
authors: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Lisa
authors: L
authors: Bishop
authors: Department of Pediatrics, Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Elizabeth A
authors: EA
authors: Sellars
authors: Department of Pediatrics, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.|Department of Ophthalmology, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.|Department of Genetics, Cell Biology and Development, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Lisa A
authors: http://orcid.org/0000-0003-3154-4249
authors: LA
authors: Schimmenti
authors: Department of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors: Natalie
authors: N
authors: Gallant
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Carlos E
authors: CE
authors: Prada
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Robert J
authors: RJ
authors: Hopkin
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Nancy D
authors: ND
authors: Leslie
authors: Department of Pediatrics, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.|Department of Ophthalmology, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.|Department of Genetics, Cell Biology and Development, Division of Genetics and Metabolism, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Susan A
authors: SA
authors: Berry
authors: Department of Human Genetics, McGill University and the Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
authors: David S
authors: DS
authors: Rosenblatt
authors: Fairview Elk River Clinic, Elk River, Minnesota, USA.
authors: Amy L
authors: AL
authors: Fair
authors: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Dietrich
authors: D
authors: Matern
authors: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Kimiyo
authors: K
authors: Raymond
authors: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Devin
authors: D
authors: Oglesbee
authors: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Piero
authors: P
authors: Rinaldo
authors: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Dimitar
authors: D
authors: Gavrilov
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000628:therapy*; D005260:Female; D006710:Homocysteine / Q000378:metabolism*; D006712:Homocystinuria / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008715:Methionine / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency; D009128:Muscle Spasticity / Q000175:diagnosis; D015997:Neonatal Screening; D011618:Psychotic Disorders / Q000175:diagnosis; D016896:Treatment Outcome
chemical_list: D006710:Homocysteine; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)