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. CONCLUSION: 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.
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. CONCLUSION: 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: Patrick R Blackburn; Raymond D Hickey; Rebecca A Nace; Nasra H Giama; Daniel L Kraft; Andrew J Bordner; Roongruedee Chaiteerakij; Jennifer B McCormick; Maja Radulovic; Rondell P Graham; Michael S Torbenson; Silvia Tortorelli; C Ronald Scott; Noralane M Lindor; Dawn S Milliner; Devin Oglesbee; Wafa'a Al-Qabandi; Markus Grompe; Dimitar K Gavrilov; Mounif El-Youssef; Karl J Clark; Paldeep S Atwal; Lewis R Roberts; Eric W Klee; Stephen C Ekker Journal: Hum Mutat Date: 2016-08-08 Impact factor: 4.878
Authors: Sebene Mayorandan; Uta Meyer; Gülden Gokcay; Nuria Garcia Segarra; Hélène Ogier de Baulny; Francjan van Spronsen; Jiri Zeman; Corinne de Laet; Ute Spiekerkoetter; Eva Thimm; Arianna Maiorana; Carlo Dionisi-Vici; Dorothea Moeslinger; Michaela Brunner-Krainz; Amelie Sophia Lotz-Havla; José Angel Cocho de Juan; Maria Luz Couce Pico; René Santer; Sabine Scholl-Bürgi; Hanna Mandel; Yngve Thomas Bliksrud; Peter Freisinger; Luis Jose Aldamiz-Echevarria; Michel Hochuli; Matthias Gautschi; Jessica Endig; Jens Jordan; Patrick McKiernan; Stefanie Ernst; Susanne Morlot; Arndt Vogel; Johannes Sander; Anibh Martin Das Journal: Orphanet J Rare Dis Date: 2014-08-01 Impact factor: 4.123
Authors: Jeffrey M Chinsky; Rani Singh; Can Ficicioglu; Clara D M van Karnebeek; Markus Grompe; Grant Mitchell; Susan E Waisbren; Muge Gucsavas-Calikoglu; Melissa P Wasserstein; Katie Coakley; C Ronald Scott Journal: Genet Med Date: 2017-08-03 Impact factor: 8.822