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性疾病。由于富马酸乙酰乙酸水解酶(FAH)的缺乏,有毒的代谢物在体内积累,导致严重的肝功能障碍,肾小管功能障碍,神经危机,和肝细胞癌的风险增加。临床症状通常在出生后开始;如果不及时治疗,患者的预后较差。琥珀酰丙酮是HT-1的特异性和敏感标志物,新生儿筛查可在无症状期早期诊断HT-1。HT-1的诊断可以基于特征性生化发现和两个等位基因基因突变的分子检测来确认。Nitisinone和低酪氨酸饮食的联合治疗可以显着改善患者的预后。在无法使用nitisinone的情况下,肝移植是一种有效的治疗方法。一些新的HT-1治疗方法正在临床试验中,包括酶替代疗法,肝细胞移植与基因靶向治疗.
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.