Santra S, Preece M A, Hulton S-A, McKiernan P J
Liver Unit, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
J Inherit Metab Dis. 2008 Jun;31(3):399-402. doi: 10.1007/s10545-008-0817-x. Epub 2008 May 23.
Tyrosinaemia type I (TTI) is an inherited deficiency in the enzyme fumarylacetoacetate hydrolase and is frequently complicated by renal tubular dysfunction which may persist in some patients after hepatic transplantation. Nitisinone has revolutionized the management of TTI but its effect on renal tubular dysfunction has not been described in a large cohort of patients.
To document the incidence and progression of renal tubular dysfunction in children with TTI treated with nitisinone at a single centre.
Twenty-one patients with TTI from a single centre were treated with nitisinone for at least 12 months. Median age at first treatment was 17 weeks (range 1 week to 27 months). Nine patients (43%) presented in acute liver failure, seven (33%) had a chronic presentation and five (24%) were detected pre-clinically.
A retrospective case analysis of plasma phosphate, urinary protein/creatinine ratio and tubular reabsorption of phosphate was performed for all patients as markers of tubular function. Renal ultrasounds were examined for evidence of nephrocalcinosis and where available, skeletal radiographs for rickets.
All patients had biochemical evidence of renal tubular dysfunction at presentation. After nitisinone and dietary treatment were started, all three markers normalized within one year. Four children had clinical rickets at presentation (which improved), of whom one had nephrocalcinosis, which did not reverse on nitisinone. No child redeveloped tubular dysfunction after commencing nitisinone. All patients with TTI had evidence of tubular dysfunction at presentation and in all cases this resolved with nitisinone and dietary control.
The tubulopathy associated with TTI is reversible.
I型酪氨酸血症（TTI）是一种遗传性的富马酰乙酰乙酸水解酶缺乏症，常并发肾小管功能障碍，在一些患者肝移植后该症状仍可能持续存在。尼替西农彻底改变了TTI的治疗方式，但尚未有大量患者队列研究描述其对肾小管功能障碍的影响。
记录在单一中心接受尼替西农治疗的TTI患儿肾小管功能障碍的发生率和进展情况。
来自单一中心的21例TTI患者接受了至少12个月的尼替西农治疗。首次治疗时的中位年龄为17周（范围1周-27个月）。9例患者（43%）表现为急性肝衰竭，7例（33%）为慢性表现，5例（24%）在临床前期被检测出。
对所有患者进行血浆磷酸盐、尿蛋白/肌酐比值及肾小管对磷酸盐重吸收情况的回顾性病例分析，以此作为肾小管功能的指标。检查肾脏超声以寻找肾钙质沉着症的证据，如有条件，检查骨骼X光片以查看佝偻病情况。
所有患者在就诊时均有肾小管功能障碍的生化证据。开始使用尼替西农和饮食治疗后，所有三项指标在一年内均恢复正常。4例患儿在就诊时有临床佝偻病（病情有所改善），其中1例有肾钙质沉着症，在使用尼替西农后未逆转。开始使用尼替西农后，没有患儿再次出现肾小管功能障碍。所有TTI患者在就诊时均有肾小管功能障碍的证据，且在所有病例中，通过尼替西农和饮食控制，该症状均得到缓解。
与TTI相关的肾小管病变是可逆的。
