title: Plasma succinylacetone is persistently raised after liver transplantation in tyrosinaemia type 1.
abstract: BACKGROUND
  Tyrosinaemia type 1 (HT1) is a rare disorder leading to accumulation of toxic metabolites such as succinylacetone (SA) and a high risk of hepatocellular carcinoma. Children with HT1 traditionally required liver transplantation (OLT) and while the need for this has been reduced by the introduction of nitisinone some still require OLT. SA inhibits the enzyme porphobilinogen (PBG) synthase and its activity can be used as a marker of active SA. Elevated urinary SA post OLT has been reported previously. This study describes a novel finding of elevated plasma SA following OLT for HT1.
  
  
  METHODS
  A retrospective analysis was performed of patients treated for HT1 at our institution from 1989-2010.
  
  
  RESULTS
  Thirteen patients had an OLT for HT1. In patients who received nitisinone prior to OLT, mean urinary and plasma SA were elevated prior to treatment but normalised by the time of OLT (p ≤ 0.01). Mean PBG synthase activity increased from 0.032 to 0.99 nkat/gHb (ref range 0.58-1.25) at the time of OLT (p < 0.01). Mean urinary SA in patients not treated with nitisinone was also elevated prior to OLT; plasma levels and PBG synthase activity were not available prior to OLT for this group. Following OLT, mean urinary and plasma SA were elevated in all for the duration of follow-up and associated with low-normal PBG synthase activity.
  
  
  CONCLUSIONS
  Urinary and plasma SA levels are elevated following OLT for HT1. Low-normal PBG synthase activity suggests the plasma SA may be active. The clinical significance of this is unclear.
authors.affiliation: NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, 5th floor IBR, Birmingham B15 2TT, UK. david_bartlett2@hotmail.com
authors.forename: David C
authors.initials: DC
authors.lastname: Bartlett
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Preece
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holme
authors.forename: Carla
authors.initials: C
authors.lastname: Lloyd
authors.forename: Phil N
authors.initials: PN
authors.lastname: Newsome
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McKiernan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003512:Cyclohexanones / Q000627:therapeutic use*; D006537:Heptanoates / Q000097:blood* / Q000652:urine; D006801:Humans; D007223:Infant; D016031:Liver Transplantation; D009579:Nitrobenzoates / Q000627:therapeutic use*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D020176:Tyrosinemias / Q000097:blood* / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*
chemical_list: D003512:Cyclohexanones; D006537:Heptanoates; D009579:Nitrobenzoates; C020804:succinylacetone; D000623:Porphobilinogen Synthase; C077073:nitisinone