遗传性酪氨酸血症Ⅰ型及其筛查和诊治进展  

Hereditary tyrosinemia typeⅠ:newborn screening,diagnosis and treatment

作　　者：唐玥 孔元原[1] TANG Yue;KONG Yuanyuan(Department of Newborn Screening,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京妇产医院北京妇幼保健院新生儿疾病筛查科,北京100020

出　　处：《浙江大学学报（医学版）》2021年第4期514-523,共10页Journal of Zhejiang University(Medical Sciences)

基　　金：国家重点研发计划(2016YFC1000304)。

摘　　要：遗传性酪氨酸血症Ⅰ型(HT-1)是因延胡索酰乙酰乙酸水解酶缺陷所致的一种常染色体隐性遗传代谢病。患者体内酪氨酸分解代谢受阻,毒性代谢物蓄积,导致严重肝功能损害、肾小管功能障碍及神经危象,患肝细胞癌风险加大。本病多于婴儿期起病,未获得及时诊治者总体预后不佳。新生儿筛查可早期发现无症状患儿,以琥珀酰丙酮作为筛查指标具有较高的特异度及敏感度。依据典型生化指标改变及分子遗传学检测结果可帮助明确诊断。尼替西农联合低酪氨酸饮食治疗可显著改善患者预后,对于没有条件使用尼替西农患者,肝移植是有效的治疗手段。酶替代疗法、肝细胞移植及基因治疗仍处于临床研究阶段,有望日后为患者提供新的治疗方案。Hereditary tyrosinemia typeⅠ(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 1 year 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 FAH 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.

关 键 词：新生儿筛查 遗传性酪氨酸血症Ⅰ型 琥珀酰丙酮 尼替西农 肝移植 综述 

分 类 号：R722.1[医药卫生—儿科]