title: Experiences during newborn screening for glutaric aciduria type 1: Diagnosis, treatment, genotype, phenotype, and outcomes.
abstract: BACKGROUND
  Glutaric aciduria type 1 (GA-1) is an organic acidemia with potentially severe neurological sequelae. In Taiwan, newborn screening (NBS) for GA-1 began in 2001, but large-scale reporting is lacking. This study describes Taiwan's largest newborn screening population to date.
  
  
  METHODS
  Between 2001 and 2015, 1,490,636 newborns were screened for GA-1. Confirmatory examinations included the carnitine loading test. Confirmed patients were treated with a low lysine diet, carnitine, and high-energy intake during illness. Clinical, laboratory, and neuroimaging data were analyzed.
  
  
  RESULTS
  Fourteen newborns were diagnosed with GA-1 (incidence: 1/106,474). C5DC concentration was clearly increased after carnitine loading in the affected newborns, but not in false-positive newborns (p = 0.004), indicating that this test is useful as an adjuvant diagnostic method. Eleven patients followed in our hospital were enrolled, namely nine NBS patients and two patients diagnosed clinically. IVS10-2A>C was the most common mutation. Two novel mutations (T36fs and N291K) were identified. Pendular nystagmus was found in two pediatric GA-1 patients. The corresponding pathology was optic atrophy in one patient, but remained undetermined in the other patient. The frequency of encephalopathic crisis decreased substantially following NBS. Among patients diagnosed by NBS, cognitive functioning was better among patients with good compliance than patients with poor compliance (p = 0.03). Abnormalities were detected by brain MRI including diffusion-weighted imaging and apparent diffusion coefficient maps; these affected various brain regions at different stages of the disease. Basal ganglion injuries occurred after an encephalopathic crisis. White matter disease was prevalent among older patients, either with or without an encephalopathic crisis.
  
  
  CONCLUSIONS
  Early diagnosis by newborn screening followed by full compliance with treatment guidelines is important to a good outcome.
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Fang-Chih
authors.initials: FC
authors.lastname: Tsai
authors.affiliation: Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Han-Jui
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department of Ophthalmology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: An-Guor
authors.initials: AG
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Hsieh
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yung-Hsiu
authors.initials: YH
authors.lastname: Lu
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ju-Shan
authors.initials: JS
authors.lastname: Pai
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Chia-Feng
authors.initials: CF
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Ting-Rong
authors.initials: TR
authors.lastname: Hsu
authors.affiliation: Physical Medicine and Rehabilitation Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chih-Jou
authors.initials: CJ
authors.lastname: Lai
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ming-Tzu
authors.initials: MT
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ping-Hsun
authors.initials: PH
authors.lastname: Ho
authors.affiliation: Department of Food and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Min-Chieh
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Physical Medicine and Rehabilitation Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ling-Yee
authors.initials: LY
authors.lastname: Cheng
authors.affiliation: Physical Medicine and Rehabilitation Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: dmniu@vghtpe.gov.tw.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D001928:Brain Diseases, Metabolic / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D005260:Female; D005838:Genotype; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency*; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D015997:Neonatal Screening; D010641:Phenotype
chemical_list: D050770:Glutaryl-CoA Dehydrogenase
keywords: Taiwan; glutaric aciduria type 1; newborn screening; nystagmus; optic atrophy