NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, 5th floor IBR, Birmingham B15 2TT, UK.
J Inherit Metab Dis. 2013 Jan;36(1):15-20. doi: 10.1007/s10545-012-9482-1. Epub 2012 Mar 29.
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.
A retrospective analysis was performed of patients treated for HT1 at our institution from 1989-2010.
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.
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.
1 型酪氨酸血症（HT1）是一种罕见的疾病，会导致有毒代谢物如琥珀酰丙酮（SA）的积累，并且肝癌风险很高。传统上，患有 HT1 的儿童需要进行肝移植（OLT），虽然尼替西农的引入减少了这种需求，但仍有一些儿童需要进行 OLT。SA 抑制酶原卟啉原（PBG）合酶，其活性可作为 SA 活性的标志物。OLT 后尿 SA 升高以前有报道。本研究描述了 HT1 患者 OLT 后血浆 SA 升高的新发现。
对我院 1989-2010 年治疗的 HT1 患者进行回顾性分析。
13 例患者因 HT1 接受 OLT。在 OLT 前接受尼替西农治疗的患者中，治疗前尿和血浆 SA 均升高，但在 OLT 时正常化（p≤0.01）。OLT 时 PBG 合酶活性从 0.032 增加到 0.99 nkat/gHb（参考范围 0.58-1.25）（p<0.01）。未接受尼替西农治疗的患者的尿 SA 也在 OLT 前升高；该组在 OLT 前未获得血浆水平和 PBG 合酶活性。OLT 后，所有患者的尿和血浆 SA 在随访期间均升高，并与低正常的 PBG 合酶活性相关。
HT1 患者 OLT 后尿和血浆 SA 水平升高。低正常的 PBG 合酶活性表明血浆 SA 可能具有活性。其临床意义尚不清楚。
