title: Two novel FAH gene mutations in a patient with hereditary tyrosinemia type I.
abstract: BACKGROUND
  Hereditary tyrosinemia type I (HT I) is a severe inborn metabolic disorder affecting the tyrosine degradation pathway. Most untreated patients die within the first two years of life. HT I results from fumarylacetoacetate hydrolase (FAH) deficiency caused by mutations in the FAH gene. The diagnosis of HT I is confirmed by measuring FAH enzyme activity in cultured fibroblasts or liver tissue and/or detecting disease-causing mutations in the FAH gene.
  
  
  METHODS
  A female neonate was referred to our hospital for further evaluation of an abnormal newborn screening test that showed elevated tyrosine levels. We analyzed amino acids and organic acids in the patient's blood and urine. To identify the genetic abnormality, all the coding exons and flanking introns of the FAH gene were analyzed via PCR.
  
  
  RESULTS
  A repeat newborn screening test and plasma amino acid analysis revealed increased tyrosine levels in the patient. Urine organic acid analysis showed increased urinary excretion of 4-hydroxyphenyllactate, 4-hydroxyphenylpyruvate, and succinylacetone. Sequence analysis of the FAH gene identified two novel variations (c.536A>G (p.Gln179Arg) and c.913+5G>A) that had not been previously reported and that were not found in 170 healthy controls.
  
  
  CONCLUSIONS
  HT I was confirmed in this patient by molecular genetic analysis of the FAH gene, with highly suggestive biochemical findings. The novel sequence variations detected in the present study should be considered disease-causing mutations by in silico analysis. In the Korean population, this is the first described case of HT I caused by a point mutation in the FAH gene.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine and Genetics, Soonchunhyang University Seoul Hospital, Seoul.
authors.forename: Hae In
authors.initials: HI
authors.lastname: Bang
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul.
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
authors.affiliation: Departments of Prosthodontics, Dentistry, Dongtan Sacred Heart Hospital, Graduated school of Clinical Dentistry, Hallym University, Seoul.
authors.forename: Mee-Ran
authors.initials: MR
authors.lastname: Shin
authors.affiliation: Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon.
authors.forename: Yong-Wha
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Soonchunhyang University College of Medicine, Seoul, Korea. nayadoo@hanmail.net ldh@schmc.ac.kr.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul nayadoo@hanmail.net ldh@schmc.ac.kr.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
mesh_terms: D000596:Amino Acids / Q000097:blood; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D007231:Infant, Newborn; D009154:Mutation; D020176:Tyrosinemias / Q000235:genetics*
chemical_list: D000596:Amino Acids; D006867:Hydrolases; C020156:fumarylacetoacetase