title: Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency.
abstract: OBJECTIVE
  Donor cell engraftment with expression of enzyme activity is the goal of liver cell transplantation for inborn errors of liver metabolism with a view to achieving sustained metabolic control.
  
  
  METHODS
  Sequential hepatic cell transplantations using male and female cells were performed in a 3.5-year-old girl with argininosuccinate lyase deficiency over a period of 5 months. Beside clinical, psychomotor, and metabolic follow-up, engraftment was analyzed in repeated liver biopsies (2.5, 5, 8, and 12 months after first infusion) by fluorescence in situ hybridization for the Y-chromosome and by measurement of tissue enzyme activity.
  
  
  RESULTS
  Metabolic control was achieved together with psychomotor catch-up, changing the clinical phenotype from a severe neonatal one to a moderate late-onset type. The child was no longer hospitalized and was able to attend normal school. Sustained engraftment of male donor liver cells was shown in repeated biopsies, reaching 19% at 8 months and 12.5% at the 12-month follow-up. XXYY tetraploid donor cells were mainly detected during the infusion period (2.5- and 5-month biopsies), whereas in the follow-up 8-month and 1-year biopsies, diploid donor cell subpopulations had become dominant. Moreover, argininosuccinate lyase activity, originally absent, became measurable in 2 different biopsy samples at 8 months, reaching 3% of control activity, indicating in situ metabolic effect and supporting the clinical evolution to a moderate form of the disease.
  
  
  CONCLUSIONS
  Liver cell transplantation can achieve donor cell engraftment in humans in a significant proportion, leading to sustained metabolic and clinical control with psychomotor catch-up.
authors.affiliation: Laboratoire d'hépatologie Pédiatrique et Transplantation Cellulaire, Département GYPE, Service de Pédiatrie, Université Catholique de Louvain & Cliniques St Luc, Brussels, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Stéphenne
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.forename: Catherine
authors.initials: C
authors.lastname: Sibille
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Nassogne
authors.forename: Françoise
authors.initials: F
authors.lastname: Smets
authors.forename: Etienne M
authors.initials: EM
authors.lastname: Sokal
mesh_terms: D000641:Ammonia / Q000097:blood; D001123:Argininosuccinate Lyase / Q000378:metabolism; D001125:Argininosuccinic Acid / Q000097:blood / Q000652:urine; D056807:Argininosuccinic Aciduria; D002657:Child Development; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008661:Metabolism, Inborn Errors / Q000503:physiopathology / Q000523:psychology / Q000601:surgery*; D011597:Psychomotor Performance; D013997:Time Factors; D018183:Transplantation Chimera; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000509:alpha-Fetoproteins; D001125:Argininosuccinic Acid; D000641:Ammonia; D001123:Argininosuccinate Lyase