浙江省新生儿异戊酸血症筛查及临床分析

目的: 了解浙江省新生儿异戊酸血症（IVA）的患病率、临床特征及基因突变特点。方法: 采用串联质谱技术对2009年1月至2019年12月浙江省新生儿疾病筛查中心的3 510 004名新生儿进行遗传代谢病筛查,结合尿有机酸分析及IVD基因检测进行IVA诊断。IVA确诊患儿进行饮食和生活管理,补充左卡尼汀和甘氨酸治疗,长期随访观察并评估患儿的生长和智能发育情况。结果: 共确诊IVA患儿15例,3例为急性新生儿型,其余无临床症状,患病率为1/234 000。所有患儿的血异戊酰基肉碱浓度均不同程度增加。12例患儿进行尿有机酸分析,其中11例异戊酰甘氨酸升高,4例伴3-羟基异戊酸升高。11例患儿进行基因检测,9例为IVD基因复合杂合突变,1例为IVD基因纯合突变,1例只检测出一个IVD基因位点。发现IVD基因突变19种（错义突变14种、内含子突变3种、移码突变1种、同义突变1种）,其中11种突变未见报道。15例患儿中1例死亡,2例在当地随访,其余暂未发现明显临床症状（随访时间2~79个月）,其中3例生长发育落后,其他患儿体格和智力发育均正常。结论: IVA临床表现无特异性,基因谱分散。使用串联质谱开展IVA新生儿筛查,实现早期诊断和治疗能纠正代谢缺陷及其引发的病理生理改变。     

威廉斯综合征25例的荧光原位杂交检测

目的通过荧光原位杂交(fluorescence in sit uhybridization,FISH)技术确诊威廉斯综合征(Williams syndrome,WS)患者,了解其临床特征,以提高临床诊断水平。方法从2004年7月至2006年6月对临床疑似的42例患者应用FISH技术检测7号染色体上弹性蛋白基因(elastin,ELN)的微缺失来确诊该病。通过详细询问病史、体检和实验室检查了解患者的临床特征。结果FISH检测结果显示25例患者存在7号染色体上的待检基因微缺失,17例患者没有检测到基因缺失。25例患者均有(100%)WS的特殊面部表象,表现为人中长,唇厚,嘴宽,眶周丰满,鼻梁扁平等。17例患者(68%)有至少一项的心血管系统疾病,包括主动脉瓣上狭窄8例(47%),其中2例(12%)合并外周肺动脉狭窄,动脉导管未闭4例(24%),高血压2例(12%),其中1例由于主动脉缩窄,主动脉瓣轻度返流2例,二尖瓣轻度返流2例。25例患者均有生长发育落后和智力发育落后,共计17例经智力测验,其中14例智商在40~53,3例智商小于40。22例患者(88%)性格热情。9例(36%)患者合并腹股沟疝。结论WS患者具有特殊面部表象,多数病例合并有心血管系统疾病并同时均具智力和生长发育落后。     

评价多重连接探针扩增法诊断染色体22q11.2微缺失结果研究

Objective To evaluate multiplex ligation-dependent probe amplification (MLPA) assay detection in analysis of chromosome 22q11.2 microdeletion. Methods Between March 2008 and September 2009, thirty-two patients including 10 males and 16 females aged between years (3.6±3.1) were selected and evaluated by history, physical examination and medical records. Of these patients, sixteen patients who were previous diagnostic as 22q11.2 microdeletion were in positive control group, the other 16 healthy children were in negative control group. All the patients were detected by MLPA and fluorescence in situ hybridization (FISH) for the presence of a 22q1 1.2 microdeletion after informed consent. Diagnostic efficacy was assessed by sensitivity, specificity and Kappa analysis. Results We have applied the two assays of detection of chromosome 22q11.2 microdeletion in 32 patients. Sixteen patients in positive control group were found to have a 22q11. 2 deletion and, with the deletion size of 3-Mb. However, as expected,chromosome 22q11.2 deletion was not found in negative control group. The MLPA results were in good agreement with that by FISH. Therefore, MLPA has high sensitivity and specificity. Conclusion MLPA is a rapid, reliable, high-throughput and relatively economical alternative to FISH technology for the diagnosis of 22q11.2 microdeletion. It can provide reliable and helpful information for clinical diagnosis of 22q11.2 microdeletion syndrome.     

评价多重连接探针扩增法诊断染色体22q11.2微缺失结果研究

Objective To evaluate multiplex ligation-dependent probe amplification (MLPA) assay detection in analysis of chromosome 22q11.2 microdeletion. Methods Between March 2008 and September 2009, thirty-two patients including 10 males and 16 females aged between years (3.6±3.1) were selected and evaluated by history, physical examination and medical records. Of these patients, sixteen patients who were previous diagnostic as 22q11.2 microdeletion were in positive control group, the other 16 healthy children were in negative control group. All the patients were detected by MLPA and fluorescence in situ hybridization (FISH) for the presence of a 22q1 1.2 microdeletion after informed consent. Diagnostic efficacy was assessed by sensitivity, specificity and Kappa analysis. Results We have applied the two assays of detection of chromosome 22q11.2 microdeletion in 32 patients. Sixteen patients in positive control group were found to have a 22q11. 2 deletion and, with the deletion size of 3-Mb. However, as expected,chromosome 22q11.2 deletion was not found in negative control group. The MLPA results were in good agreement with that by FISH. Therefore, MLPA has high sensitivity and specificity. Conclusion MLPA is a rapid, reliable, high-throughput and relatively economical alternative to FISH technology for the diagnosis of 22q11.2 microdeletion. It can provide reliable and helpful information for clinical diagnosis of 22q11.2 microdeletion syndrome.     

伴先天性甲状腺功能减低症的威廉斯综合征二例

例1女,3岁5个月,因"新生儿疾病筛查发现促甲状腺激素(TSH)增高2 d"来本院筛查门诊.无不适主诉.第1胎第1产,胎龄40周,自然分娩,出生体重2.4 kg.否认家族遗传病史.查体发现心前区Ⅱ/6级收缩期杂音.甲状腺功能检查:TSH＞75 mU/L,总四碘甲腺原氨酸(T4)、游离四碘甲腺原氨酸(FT4)降低,分别为41.2 nmol/L、6.5 pmol/L.总三碘甲腺原氨酸(T3)及游离三碘甲腺原氨酸(FT3)均正常,甲状腺抗体均阴性.     

重症联合免疫缺陷病X-连锁无丙种球蛋血症及脊髓性肌萎缩症新生儿筛查研究进展

重症联合免疫缺陷病（SCID）、X-连锁无丙种球蛋白血症（XLA）和脊髓性肌萎缩症（SMA）是严重影响儿童健康甚至导致死亡的遗传性出生缺陷。早期筛查、早期诊断及早期治疗是改善预后、降低病死率的关键。新生儿筛查是实现早期诊治的有效手段,部分国家和地区已将这3种疾病纳入新生儿筛查的范围。开展3种疾病的新生儿联合筛查,可优化筛查的成本效益。