Department of Newborn Screening, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100020, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Aug 25;50(4):514-523. doi: 10.3724/zdxbyxb-2021-0255.
Hereditary tyrosinemia type Ⅰ (HT-1) is a severe autosomal recessive inherited metabolic disease. Due to the deficiency of fumarylacetoacetase hydrolase (FAH), the toxic metabolites are accumulated in the body, resulting in severe liver dysfunction, renal tubular dysfunctions, neurological crises, and the increased risk of hepatocellular carcinoma. Clinical symptoms typically begin at after the birth; the prognosis of patients is poor if they are not treated timely. Succinylacetone is a specific and sensitive marker for HT-1, and the screening in newborns can make early diagnosis of HT-1 at the asymptomatic stage. The diagnosis of HT-1 can be confirmed based on the characteristic biochemical findings and molecular testing of mutations in both alleles of gene. Combined treatment with nitisinone and a low tyrosine diet may significantly improve outcomes for patients. Liver transplantation is an effective treatment in cases where nitisinone is not available. Some novel HT-1 treatments are in clinical trials, including enzyme replacement therapy, hepatocyte transplantation and gene-targeted therapy.
遗传性酪氨酸血症Ⅰ型（HT-1）是一种严重的常染色体隐性遗传代谢疾病。由于延胡索酰乙酰乙酸水解酶（FAH）的缺乏，有毒代谢物在体内蓄积，导致严重的肝肾功能障碍、肾小管功能障碍、神经危机以及肝细胞癌的风险增加。临床症状通常在出生后出现；如果不及时治疗，患者的预后很差。琥珀酰丙酮是 HT-1 的特异性和敏感标志物，对新生儿进行筛查可以在无症状期早期诊断 HT-1。HT-1 的诊断可基于特征生化发现和基因突变的分子检测。尼替西农联合低酪氨酸饮食治疗可能显著改善患者的预后。在无法使用尼替西农的情况下，肝移植是一种有效的治疗方法。一些新型 HT-1 治疗方法正在临床试验中，包括酶替代疗法、肝细胞移植和基因靶向治疗。
