Introduction Tyrosinaemia type 1 (TT1) is a rare disorder of tyrosine metabolism leading to accumulation of toxic metabolites such as succinylacetone (SA) and a high risk of hepatocellular carcinoma. Children with TT1 traditionally required liver transplantation (OLT) and while the need for this has reduced since the introduction of nitisinone some still go on to require OLT. Circulating SA inhibits the enzyme porphobilinogen (PBG) synthase and its activity can be used as a marker of functional circulating SA. Elevated urinary SA post OLT thought to be due to local production has been reported.
Aim This study describes a novel finding of elevated plasma SA following OLT for TT1.
Method A retrospective analysis was performed of patients treated for TT1 at our institution from 1989 to 2010.
Results In patients who received nitisinone prior to OLT mean urinary SA was elevated at presentation (159.6 mmol/mol creatinine, ref. range <1) as was plasma SA (17.58 mol/l, ref. range <0.01) but both became undetectable on nitisinone prior to OLT (p<0.05). This was associated with increased mean PBG synthase activity from 0.032 to 0.99 nkat/g Hb (ref. range 0.58 1.25). In patients who did not receive nitisinone, mean urinary SA was 274.6 mmol/mol creatinine immediately prior to transplant. Plasma SA levels/PBG synthase activity prior to OLT were not available in this group. Following OLT in patients treated with nitisinone, mean urinary SA levels quickly rose and remained elevated for the duration of follow-up. Plasma SA levels also rose with a progressive decrease in mean PBG synthase activity to low-normal levels. In patients who had not received nitisinone, mean urinary SA fell quickly by 1 year post OLT but remained above normal at levels similar to those seen in the nitisinone treated group. No data were available for plasma SA/PBG synthase activity in this group until 13 years post OLT. However, from this point onwards mean plasma SA remained elevated with a low-normal PBG synthase activity similar to that seen in nitisinone treated patients. There was no apparent correlation between SA levels and renal function. Despite reduced PBG synthase levels, no patients developed porphyria-like symptoms.
Conclusion Urinary and plasma SA levels are elevated following OLT for TT1. Low-normal PBG synthase activity suggests the circulating SA may be functional. The clinical significance of this is unclear.
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