Dweikat Imad, Qawasmi Nada, Najeeb Aysha, Radwan Mohammad
Metabolic Department Arab American University, PO Box 240 Jenin, 13 Zababdeh, Palestine.
Pediatric Department, Makassed Hospital, Palestine.
Metabol Open. 2021 Jan 28;9:100083. doi: 10.1016/j.metop.2021.100083. eCollection 2021 Mar.
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.
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.
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.
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.
1型酪氨酸血症（肝肾型酪氨酸血症，HT1）是一种罕见的常染色体隐性遗传性酪氨酸代谢病，由酪氨酸分解代谢途径中的最后一种酶——富马酰乙酰乙酸水解酶（FAH）缺乏所致，若不治疗会导致严重的肝脏、肾脏和周围神经损伤。早期治疗可预防急性肝衰竭、肾功能不全、肝硬化、肝细胞癌（HCC）并提高生存率。
基于过去25年中诊断出的25例巴勒斯坦HT1患者的临床和生化表现、治疗及预后进行了一项回顾性单中心研究。
巴勒斯坦的新生儿筛查项目中未包括HT1。诊断时的平均年龄为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、血清转氨酶和凝血酶原时间升高，血清磷降低而碱性磷酸酶升高，符合继发于肾小管功能障碍的低磷性佝偻病。所有患者均接受尼替西农治疗。尼替西农治疗的平均持续时间为74个月，平均剂量为0.89毫克/千克/天。无一例发生HCC或神经危机。
大多数患者表现为肝衰竭和肾小管功能障碍。尼替西农治疗对所有患者均有效，改善了HT1的短期和长期预后。在开始使用尼替西农的第一周内，所有患者的肾小管功能障碍均得到改善。早期诊断很有必要，因为治疗延迟会增加进行性肝衰竭、HCC、进行性肾病和神经病变的风险。
