title: Liver transplantation for lethal genetic syndromes: a novel model of personalized genomic medicine.
abstract: BACKGROUND
  Our aim was to analyze our single-center experience with orthotopic liver transplantation for metabolic lethal genetic syndromes in children and adults.
  
  
  METHODS
  From 1984 to 2012, all pediatric (younger than 18 years) and adult (18 years and older) patients who underwent orthotopic liver transplantation for lethal genetic disorders were identified. Data on diagnostic pathways and specific outcomes were analyzed for both groups. Outcomes measures included recurrence rate as well as graft and patient survival.
  
  
  RESULTS
  Metabolic lethal genetic syndrome was the primary indication for orthotopic liver transplantation in 152 of 4,564 patients (3.3%) at University of California, Los Angeles during the study period (74 pediatric patients and 78 adults). Genetic testing was performed in only 12% of the 152 patients and in 39% of patients after 2006. Two patients (1.3%) experienced a recurrence of the genetic disease. Overall 5- and 20-year survival rates were 89% and 77% for children and 73% and 50% for adults. Survival of pediatric patients was superior to adults (log-rank p < 0.009). Multivariate analysis identified age (hazard ratio = 2.18), preoperative life support (hazard ratio = 2.68), and earlier transplantation (hazard ratio = 3.41) as independent predictors of reduced survival.
  
  
  CONCLUSIONS
  Orthotopic liver transplantation achieved excellent long-term survival in pediatric and adult patients with lethal genetic syndromes and represents a model of personalized genomic medicine by providing gene therapy through solid organ transplantation.
authors.affiliation: Department of Surgery, The Dumont-UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7054, USA. henrik.petrowsky@usz.ch
authors.forename: Henrik
authors.initials: H
authors.lastname: Petrowsky
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
authors.forename: Voon Meng
authors.initials: VM
authors.lastname: Leow
authors.forename: Robert S
authors.initials: RS
authors.lastname: Venick
authors.forename: Vatche
authors.initials: V
authors.lastname: Agopian
authors.forename: Fady M
authors.initials: FM
authors.lastname: Kaldas
authors.forename: Ali
authors.initials: A
authors.lastname: Zarrinpar
authors.forename: Daniela
authors.initials: D
authors.lastname: Markovic
authors.forename: Sue V
authors.initials: SV
authors.lastname: McDiarmid
authors.forename: Johnny C
authors.initials: JC
authors.lastname: Hong
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Farmer
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Hiatt
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000601:surgery*; D015316:Genetic Therapy; D023281:Genomics; D006801:Humans; D007223:Infant; D008107:Liver Diseases / Q000235:genetics* / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D057285:Precision Medicine / Q000379:methods*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013577:Syndrome; D055815:Young Adult