上海地区遗传性酪氨酸血症Ⅰ型的筛查及临床、遗传学特点分析  

Screening and analysis of clinical and genetic characteristics of hereditary tyrosinemia type I in Shanghai area

作　　者：纪伟 田国力 王燕敏 张潇分 周卓 郭静 Ji Wei;Tian Guoli;Wang Yanmin;Zhang Xiaofen;Zhou Zhuo;Guo Jing(Department of Neonatal Screening Center,Shanghai Children′s Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200040,China)

机构地区：[1]上海市儿童医院、上海交通大学医学院附属儿童医院新生儿筛查中心,上海200040

出　　处：《中国医师杂志》2025年第1期76-80,共5页Journal of Chinese Physician

基　　金：上海市重中之重临床重点专科建设项目(2017ZZ02019);上海交通大学"交大之星"计划医工交叉研究项目(YG2022QN097);上海市科委项目(22Y11906900);上海市儿童医院国家自然科学基金培育专项(2021YGZQ09)。

摘　　要：目的探讨遗传性酪氨酸血症Ⅰ型(HT-Ⅰ)在上海部分地区的筛查,分析临床、遗传学特点及预后,同时总结国内外报道中国患儿病例的相关特点。方法回顾性分析2010年12月—2023年5月在上海市儿童医院新生儿筛查中心经串联质谱遗传代谢病筛查结合基因检测诊断为HT-Ⅰ患儿的临床资料,并对相关文献进行复习。结果282149例新生儿进行串联质谱遗传代谢病筛查,确诊HT-Ⅰ患儿1例,发病率为1∶282149。基因检测发现FAH基因c.974C>T和c.22G>T复合杂合突变,其中c.22G>T为未报道新发变异。明确诊断后立即给予饮食及药物治疗,目前随访至8个月,体格、智力发育均正常。数据库检索共获得符合纳入标准的文献32篇,报道46例HT-Ⅰ中国患儿,临床表现多为腹胀、纳差、黄疸等,伴有不同程度的凝血功能异常、肝脾肿大、肝硬化甚至肝衰竭。共报道25种等位基因,c.455G>A变异最为常见。结论HT-Ⅰ在中国上海地区的人群中罕见,新发变异丰富了HT-Ⅰ变异谱,为患儿家系遗传咨询和产前诊断提供依据。Objective To investigate the screening,clinical and genetic characteristics and prognosis of hereditary tyrosinemia typeⅠ(HT-Ⅰ)in some areas of Shanghai,and to summarize the relevant characteristics of Chinese cases reported at home and abroad.MethodsFrom December 2010 to May 2023,the clinical data of children diagnosed with HT-Ⅰby tandem mass spectrometry combined with genetic detection in Neonatal Screening Center of Shanghai Children′s Hospital were retrospectively analyzed,and the relevant literature was reviewed.ResultsA total of 282149 neonates were screened for genetic metabolic disease by tandem mass spectrometry,and 1 case of HT-Ⅰwas diagnosed,with an incidence of 1∶282149.Complex heterozygous mutations of FAH genes c.974C>T and c.22G>T were found by genetic testing.c.22G>T was not reported as a new mutation.Diet and drug therapy were given immediately after diagnosis.At present,the follow-up was up to 8 months,and the physical and intellectual development were normal.A total of 32 literatures meeting the inclusion criteria were obtained through database search,and 46 cases of HT-ⅠChinese children were reported.Most of the clinical manifestations were abdominal distension,poor appetite,jaundice,etc.,accompanied by different degrees of abnormal coagulation function,hepatosplenomegalysis,cirrhosis and even liver failure.A total of 25 alleles were reported,and the variation of c.455G>A was the most common.ConclusionsHT-Ⅰis rare in the population of Shanghai,China,and new mutations enrich the variation spectrum of HT-Ⅰ,which provides basis for family genetic counseling and prenatal diagnosis of children.

关 键 词：新生儿筛查 遗传性酪氨酸血症Ⅰ型 

分 类 号：R722.1[医药卫生—儿科]