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Abstract：
BACKGROUND: Tyrosinemia type 1 (hepatorenal tyrosinemia, HT1) is a rare autosomal recessive inborn error of tyrosine metabolism caused by deficiency of the last enzyme in the tyrosine catabolic pathway, fumarylacetoacetate hydrolase (FAH) leading to severe hepatic, renal and peripheral nerve damage if left untreated. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival.
METHODS: A retrospective single center study was carried out based on the clinical and biochemical presentation, therapy and outcome of 25 Palestinian patients with HT1 diagnosed during the last 25 years.
RESULTS: HT1 is not included in newborn screening program in Palestine. The mean age at diagnosis was 8 months and the main clinical manifestations were coagulopathy, hepatomegaly, splenomegaly and renal tubular dysfunction. The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. All patients were treated with nitisinone. The mean duration of nitisinone treatment was 74 months and the mean dosage was 0.89 mg/kg/day. None developed HCC or neurological crisis.
CONCLUSIONS: Most patients present with liver failure and renal tubular dysfunction. Nitisinone treatment was effective therapy in all patients and improved both short- and long-term prognosis of HT1. Renal tubular dysfunction improved in all patients within the first week of starting nitisinone. Early diagnosis is necessary because delay in the treatment increases the risk of progressive liver failure HCC, progressive renal disease and neuropathy.
METHODS: A retrospective single center study was carried out based on the clinical and biochemical presentation, therapy and outcome of 25 Palestinian patients with HT1 diagnosed during the last 25 years.
RESULTS: HT1 is not included in newborn screening program in Palestine. The mean age at diagnosis was 8 months and the main clinical manifestations were coagulopathy, hepatomegaly, splenomegaly and renal tubular dysfunction. The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. All patients were treated with nitisinone. The mean duration of nitisinone treatment was 74 months and the mean dosage was 0.89 mg/kg/day. None developed HCC or neurological crisis.
CONCLUSIONS: Most patients present with liver failure and renal tubular dysfunction. Nitisinone treatment was effective therapy in all patients and improved both short- and long-term prognosis of HT1. Renal tubular dysfunction improved in all patients within the first week of starting nitisinone. Early diagnosis is necessary because delay in the treatment increases the risk of progressive liver failure HCC, progressive renal disease and neuropathy.
摘要：
背景：酪氨酸血症1型（肝肾酪氨酸血症，HT1）是一种罕见的常染色体隐性遗传先天性酪氨酸代谢错误，由酪氨酸分解代谢途径中的最后一种酶缺乏引起，富马酸乙酰乙酸水解酶（FAH）导致严重的肝脏，如果不治疗，肾脏和周围神经损伤。早期治疗可以预防急性肝衰竭，肾功能不全,肝硬化,肝细胞癌（HCC）和提高生存率。
方法：根据临床和生化表现进行回顾性单中心研究，在过去25年中诊断为HT1的25名巴勒斯坦患者的治疗和结果。
结果：HT1不包括在巴勒斯坦的新生儿筛查计划中。诊断时平均年龄为8个月，主要临床表现为凝血病，肝肿大,脾肿大和肾小管功能障碍。主要生化异常为血浆酪氨酸升高,血清转氨酶和凝血酶原时间，和低血清磷，碱性磷酸酶升高，与继发于肾小管功能障碍的低磷血症病相容。所有患者均接受尼替辛酮治疗。尼替辛酮治疗的平均持续时间为74个月，平均剂量为0.89mg/kg/天。没有人发生HCC或神经系统危象。
结论：大多数患者表现为肝衰竭和肾小管功能障碍。Nitisinone治疗是所有患者的有效治疗方法，可改善HT1的短期和长期预后。在开始使用尼替辛酮的第一周内，所有患者的肾小管功能障碍均得到改善。早期诊断是必要的，因为延迟治疗会增加进行性肝衰竭HCC的风险，进行性肾脏疾病和神经病变。
方法：根据临床和生化表现进行回顾性单中心研究，在过去25年中诊断为HT1的25名巴勒斯坦患者的治疗和结果。
结果：HT1不包括在巴勒斯坦的新生儿筛查计划中。诊断时平均年龄为8个月，主要临床表现为凝血病，肝肿大,脾肿大和肾小管功能障碍。主要生化异常为血浆酪氨酸升高,血清转氨酶和凝血酶原时间，和低血清磷，碱性磷酸酶升高，与继发于肾小管功能障碍的低磷血症病相容。所有患者均接受尼替辛酮治疗。尼替辛酮治疗的平均持续时间为74个月，平均剂量为0.89mg/kg/天。没有人发生HCC或神经系统危象。
结论：大多数患者表现为肝衰竭和肾小管功能障碍。Nitisinone治疗是所有患者的有效治疗方法，可改善HT1的短期和长期预后。在开始使用尼替辛酮的第一周内，所有患者的肾小管功能障碍均得到改善。早期诊断是必要的，因为延迟治疗会增加进行性肝衰竭HCC的风险，进行性肾脏疾病和神经病变。
