title: 3-O-methyldopa levels in newborns: Result of newborn screening for aromatic l-amino-acid decarboxylase deficiency.
abstract: The diagnosis of aromatic l-amino-acid decarboxylase (AADC) deficiency is often delayed because a cerebrospinal fluid analysis is required to detect a neurotransmitter deficiency. We here demonstrated that an elevated concentration of l-dopa metabolite 3-O-methyldopa (3-OMD) in dried blood spots could be integrated into newborn screening program to precisely predict AADC deficiency.
  
  
  
  After obtaining parental consent, an additional spot was punched from newborn filter paper, eluted, cleaned, and analyzed by tandem mass spectrometry. Newborns with a 3-OMD concentration exceeding 500ng/mL were referred for confirmatory testing.
  
  
  
  From September 2013 to December 2015, 127,987 newborns were screened for AADC deficiency. The mean 3-OMD concentration in these newborns was 88.08ng/mL (SD=27.74ng/mL). Four newborns exhibited an elevated 3-OMD concentration (range, 939-3241ng/mL). All four newborns were confirmed to carry two pathologic DDC mutations, indicating an incidence of AADC deficiency of 1:32,000. During the follow-up period, three patients developed typical symptoms of AADC deficiency. Among 16 newborns with mildly elevated 3-OMD levels, six were heterozygous for the DDC IVS6+4A>T mutation.
  
  
  
  Newborn screening of AADC deficiency was achieved with a 100% positive-predictive rate. An association for gestational age could be further elucidated.
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pin-Wen
authors.initials: PW
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ni-Chung
authors.initials: NC
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wu-Shiun
authors.initials: WS
authors.lastname: Hsieh
authors.affiliation: Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Pao-Chin
authors.initials: PC
authors.lastname: Chiu
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: hwuwlntu@ntu.edu.tw.
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.affiliation: Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Buddhist Tzu-Chi General Hospital, Taiwan.
authors.forename: Shao-Yin
authors.initials: SY
authors.lastname: Chu
authors.affiliation: Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.affiliation: Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Mei-Chyn
authors.initials: MC
authors.lastname: Chao
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D018377:Neurotransmitter Agents / Q000097:blood; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018377:Neurotransmitter Agents; D014443:Tyrosine; D001142:Aromatic-L-Amino-Acid Decarboxylases; C008404:3-methoxytyrosine
keywords: 3-O-methyldopa; AADC; Aromatic l-amino-acid decarboxylase; Newborn screening