溶酶体贮积症1 520例疾病谱分析

目的分析上海市单中心溶酶体贮积症(LSDs)疾病谱, 探讨不同类型LSDs的流行分布情况。方法回顾性分析。纳入2008年8月至2022年5月在上海交通大学医学院附属新华医院就诊的疑似LSDs患者5 476例, 其中男3 415例, 女2 061例;中位年龄为4岁(1 d至72岁), 利用荧光底物法和生物化学法检测不同溶酶体酶的活性。结果共确诊LSDs患者1 520例, 其中男972例, 女548例;中位年龄为4岁(1 d至59岁);包含19种亚型。黏多糖贮积症(MPS)最常见, 占比为45.46%(691/1 520), 其次为鞘脂贮积病和糖原累积病Ⅱ型, 占比分别为33.88%(515/1 520)和16.05%(244/1 520)。对于MPS, MPS Ⅱ型最常见, 占比为45.73%(316/691), MPS ⅣA型次之, 占比22.87%(158/691)。尼曼匹克A/B型、戈谢病和球型细胞脑白质营养不良在鞘脂贮积病中常见, 占比分别为37.09%(191/515)、34.37%(177/515)和10.29%(53/515)。结论 LSDs为常见的遗传代谢病, 尤其是MP...     

溶酶体贮积症

溶酶体贮积症(LSDs)是一组较常见的遗传性代谢病,其新生儿发生率为1/7000~1/8000。但很多医师对这组疾病认识不够,以致常有患儿被延误诊断。有的医师给患儿家长咨询错误指导,其结果常是再次妊娠,又出生一个有同样疾病的患儿。近年来国外对这组疾病的治疗有较大进展,因此认识这组疾病并能早期诊断、干预是很重要的。本文介绍常见的LSDs的临床表现。     

神经鞘脂贮积病(英文)

目的建立一系列能够确诊神经鞘脂贮积病溶酶体酶活性的测定方法,收集神经鞘脂贮积病发病率方面的数据,为神经鞘脂贮积病的产前诊断打下基础,以降低其出生率。方法在小儿内分泌和遗传代谢病门诊收集疑似神经鞘脂贮积病患者的外周血,用右旋糖苷分离白细胞,然后有选择地测定溶酶体酶活性。其中测定酸性β-葡萄糖苷酶、酸性鞘磷脂酶、半乳糖脑苷脂酶及β-半乳糖苷酶活性使用的是其相应的人工合成荧光底物,测定芳香硫脂酶A活性使用的是比色底物2-羟基-5-硝基苯硫酸氢二钾盐。结果在1年内共检测到17例患儿,分别属于5种不同的神经鞘脂贮积病,包括3例戈谢病、9例尼曼匹克病A/B型、2例异染性脑白质营养不良、2例Krabbe病和1例GM1神经节苷脂贮积病。结论与国外资料比较,国内神经鞘脂贮积病诊断的病例明显偏少,在临床工作中需加强对此类疾病的认识。     

溶酶体贮积症的骨改变

遗传代谢病（inherited metabolic disorders,IMD）是一大类以生化代谢通路中的酶、辅酶或转运体等功能缺陷为特征的单基因遗传病,已命名的IMD近1500种。溶酶体贮积症是由于溶酶体内多种酶、酶激活因子或溶酶体膜蛋白基因变异所致的一大类以多系统损害为特征的遗传代谢病。以黏多糖贮积症为代表的多种溶酶体贮积症可出现特征性的多发性骨发育代谢障碍。该文简要介绍一些以骨改变为特征的溶酶体贮积症。     

黏多糖贮积症47例的常见酶学分型

目的 对临床疑似黏多糖贮积症患儿进行常见酶学分型.方法 收集70例临床疑似黏多糖贮积症的患儿,临床疑似黏多糖贮积症的指征包括:生长落后,丑陋面容,骨骼畸形,肝脾增大,智力落后,关节僵硬/松弛等.收集疑似黏多糖贮积症患儿外周血,分离白细胞后,用人工荧光底物法和生物化学方法,分别检测导致Ⅰ,Ⅱ,ⅣA,ⅣB,Ⅵ及Ⅶ缺陷的酶,α-L-艾杜糖酶,艾杜糖醛酸硫酸酯酶,半乳糖胺-6-硫酸硫酸酯酶,β-半乳糖苷酶,芳基硫酸酶酶B及β葡萄糖醛酸酶的活性.结果 在70例可疑患儿中,共确诊黏多糖贮积症47例,其中Ⅰ型7例(占确诊黏多糖贮积症例数的15%),Ⅱ型28例(59%),ⅣA型12例(26%),未发现ⅣB,Ⅵ及Ⅶ型的患儿.黏多糖贮积症Ⅱ型患儿临床表型多样,ⅣA型患儿中67%有典型的关节松弛表现.结论 Ⅱ型可能是中国人黏多糖贮积症中最主要的一型,其他较常见的是ⅣA型和Ⅰ型.     

造血干细胞移植治疗黏多糖贮积症Ⅱ型代谢指标分析

目的从实验室代谢指标探讨黏多糖贮积症Ⅱ型患儿造血干细胞移植治疗后的疗效。方法回顾分析23例男性黏多糖贮积症Ⅱ型患儿造血干细胞移植治疗年龄及治疗前后外周血白细胞艾杜糖醛酸-2-硫酸酯酶(IDS)活性、尿黏多糖(GAG)定性和电泳结果变化。结果 23例男性患儿,移植中位年龄为4.5岁(1.75～12岁)。移植前23例患儿IDS活性均显著低于正常值;移植后100天,90.9%(20/22)患儿IDS活性达到正常值;至移植后2年,100%(9/9)患儿IDS活性达到正常值;移植2年后,患儿IDS活性稳定于正常值范围。移植后2年内患儿IDS活性数值变化差异无统计学意义(P0.05)。移植后100天即有53.3%(8/15)患儿尿GAG含量较移植前下降。截止到资料收集时间,75.0%(15/20)患儿移植后尿GAG含量较移植前下降,但仅2例(10.0%,2/20)患儿移植后尿GAG完全转阴。结论造血干细胞移植治疗可恢复黏多糖贮积症Ⅱ型患儿外周血白细胞IDS活性至正常值,但对于降低黏多糖贮积症Ⅱ型患儿尿GAG含量作用有限,其可在一定程度上降低尿GAG含量但大多未至正常水平。     

儿童Ⅰ型糖原贮积病的消化道特征北大核心CSCD

目的了解儿童Ⅰ型糖原贮积病(Ⅰ型GSD)的消化道特征, 为临床多学科联合管理提供依据。方法 2020年6月至12月收集经基因检测确诊为Ⅰ型GSD, 年龄为0~18岁临床数据完整的来自全国各个省市, 包括北京、上海、广东、广西、湖南、四川、云南、贵州、河南、河北、浙江、江苏、陕西、安徽、黑龙江的儿童患者。采用横断面问卷调查方式。结果总计回收52份问卷, 符合纳入标准并有完整资料43例, 其中Ⅰa型9例, Ⅰb型34例;男30例(69.8%), 女13例(30.2%);年龄为1~18岁;家中兄弟姐妹同样确诊为Ⅰ型GSD 7例(16.3%), 均为Ⅰb型。消化道表现为反复腹泻26例(60.5%), 肛周病变(红斑、溃疡、脓肿)25例(58.1%), 腹痛/腹胀24例(55.8%), 恶心/呕吐22例(51.1%), 黏液便/血便14例(32.6%);至少2个以上消化道症状者38例(88.0%);反复口腔炎及口腔溃疡者33例(76.7%)。血常规白细胞总数<4.0×109/L者24例(55.8%), 中性粒细胞绝对值<1.5×109/L者19例(44.2%), 其中<0.5×109/L 10例(23.3%), 白细胞总数及中性粒细胞绝对值降低者均为Ⅰb型GSD患儿。血小板(PLT)>300×109/L 30例(69.8%)。18例Ⅰb型GSD患儿行胃肠镜检查, 诊断GSD相关性肠病16例。饮食添加生玉米淀粉39例(90.7%);麦芽糊精3例(6.9%);特殊医学配方19例(44.2%)。Ⅰb型GSD患儿因粒细胞低下及功能障碍需要反复应用抗生素20例, 应用粒细胞集落刺激因子(G-CSF)15例, 其中11例诊断为GSD相关性肠病。结论儿童Ⅰ型GSD的消化道症状常见, 尤以Ⅰb型GSD显著, 此型患儿GSD相关性肠病发生率高, 应用G-CSF不能避免肠病的发生, 其发病机制有待进一步研究。饮食疗法是Ⅰ型GSD的一线治疗, 多学科联合管理, 有助于减少患儿的并发症, 提高患儿的生活质量。     

外周血淋巴细胞异常空泡检查对溶酶体贮积病筛查和诊断的价值

目的 探讨外周血淋巴细胞空泡检查在溶酶体贮积病的筛查和诊断中的应用价值.方法 对2008年1月至2009年12月在我院接受外周血淋巴细胞光镜和电子显微镜检查的疑诊溶酶体贮积病患儿的临床和病理资料进行回顾性分析.结果 本组42例患儿均为隐匿起病,均存在进行性智力运动发育落后或倒退,其中32例伴抽搐,3例视力下降,4例肝脾大.本组均接受外周血涂片检查,其中14例外周血淋巴细胞存在异常空泡,这14例中8例经进一步检查确诊为溶酶体贮积病,包括4例淋巴细胞超微结构检查发现曲线体,确诊为神经元蜡样质脂褐质沉积症;2例经酶活性测定分别确诊为异染性脑白质营养不良和糖原累积症Ⅱ型,2例依据骨髓涂片和鞘磷脂酶活性检查诊断为尼曼-匹克病C型;6例未能明确诊断.结论 由于方法简单且微创,外周血淋巴细胞异常空泡检查可以用于溶酶体贮积病的筛查.对于疑诊为神经元蜡样质脂褐质沉积症的病例,外周血淋巴细胞超微结构检查有可能提供确诊依据.

Abstract：

Objective Lysosomal storage diseases are a group of inherited disorders caused by deficiency of lysosomal enzymes or structural components. The manifestations of lysosomal storage diseases are complicated due to different enzyme deficiency. It has been reported that a range of metabolic diseases resulting in abnormal accumulation of metabolic byproducts may exhibit abnormal cytoplasmic vacuolation of lymphocytes. The aim of this study was to elicit the usefulness of vacuolated peripheral lymphocytes detection in screening and diagnosis of lysosomal storage diseases. Method Clinical data of 42 patients who underwent microscopic and electron microscopic examination of peripheral blood specimens in our department were retrospectively evaluated between January 2008 and December 2009. Result Forty-two patients with the suspected lysosomal storage diseases were included, these patients presented with motor and developmental retardation and/or regression. Seizure occurred in 32 patients. Hepatosplenomegaly were found in 4 patients. Three patients presented with declined visual acuity. Atrophy and/or abnormal signals were detected on cranial CT/MRI images in 24 patients. Blood biochemical tests were normal. Serum levels of ammonia, lactic acid and pyruvate were normal. Serum amino acid profiles and urinary organic acid profiles were normal. Serum fatty acid profiles were normal. Vacuolated lymphocytes were detected on microscopic examination of blood film in 14 patients, and 8 of these patients were confirmed to have lysosomal storage disease. Curvilinear body was found on electronic microscopic examination of peripheral lymphocytes specimens in 4 patients, confirming the diagnosis of neuronal ceroid lipofuscinosis. In 3 of these 4 patients, curvilinear body were also found on electronic microscopic examination of skin and/or muscle specimens. Enzyme analysis confirmed the diagnosis of metachromatic leukodystrophy in one patient and Pompe's disease in another patient. Typical pathological changes were found on the examination of bone marrow in 2 patients with normal acid sphingomyelinase activity. So the patients were diagnosed with Niemann-Pick disease type C. The diagnosis of other 6 patients with vacuolated lymphocytes was unknown.Conclusion Because of its usefulness and minimal invasiveness, vacuolated peripheral lymphocytes examination should be a screening test for lysosomal storage disease. As for patients with suspected neuronal ceroid lipofuscinosis, electron microscopic examination of peripheral lymphocyte specimens may provide specific clues to the final diagnosis.     

35例黏多糖贮积症Ⅳ型患儿临床特点及酶学诊断

目的总结中国人黏多糖贮积症(MPS)Ⅳ型的临床特点及酶学诊断,提供MPS鉴别诊断要点。方法对2006年6月至2011年11月因矮小伴有多发骨骼畸形就诊并诊断为MPSⅣ型患儿的临床特点、骨骼影像学、尿黏多糖定性电泳及酶活性检测结果进行回顾分析。结果 35例患儿诊断为MPSⅣ型(ⅣA型34例,ⅣB型1例),所有患儿具有不同程度的MPSⅣ型临床特点,包括矮小、脊柱发育不良、关节畸形,但智能发育正常;脊柱X线显示,胸腰椎椎体前缘鸟嘴样改变及肋骨飘带状等;80%患儿的尿液黏多糖定性阳性,尿液黏多糖电泳显示CS区带;34例MPSⅣA型患儿白细胞半乳糖胺-6-硫酸盐硫酸酯酶(GALNS)活性极低[(0.85±1.33)nmol/(17 h.mg)],1例MPSⅣB型患儿β-半乳糖苷酶(GLB1)酶活性极低[5.03 nmol/(mg.h)]。结论对临床高度怀疑MPS的患儿,可检测尿液黏多糖进行初步筛查,再以酶活性分析来确诊。     

GNPTAB 基因突变致黏脂贮积症II 和 III α/β 3 例报告并文献复习

目的分析临床罕见的黏脂贮积症(ML)II和 III α/β的临床特征及基因特点。方法回顾分析3例GNPTAB基因变异致ML II和 III α/β患儿的临床资料,并复习相关文献。结果 2例患儿为同一家系汉族男性,分别为8岁3个月和23个月,有不同程度的关节挛缩和矮小;另1例患儿为女性,19个月,生长发育迟缓,面容特殊,眼眶浅、鼻梁塌陷、嘴巴突出、耳位低等,反复呼吸道感染。基因检测显示2例男性患儿均有GNPTAB基因的复合杂合变异c.1284+1GT;c.1370CT(p.Pro436Leu);女性患儿有GNPTAB基因的纯合变异c.1090CT(p.Arg364*)。3例患儿的父母均携带GNPTAB基因的杂合变异。结论 GNPTAB基因变异可致ML II和 III α/β,临床应注意两者的区分。     

婴儿型GM1神经节苷脂贮积症2例临床及遗传学特点北大核心CSCD

目的对2例婴儿型GM1神经节苷脂贮积症患儿临床及遗传学特点进行总结。方法收集2019年5月至6月天津市儿童医院康复科收治的2例婴儿型GM1神经节苷脂贮积症患儿临床资料,分析其临床及遗传学特点。结果2例患儿主要表现为婴儿期发病;精神运动发育落后,并有倒退;粗笨面容;对声音敏感;牙龈增厚;牙齿萌出异常;肌张力低下或肌张力障碍;骨发育不良;皮肤异常。例1肝脾大,角膜混浊,多发关节挛缩;例2眼底樱桃红斑,癫痫发作。生化检查均提示碱性磷酸酶显著增高,谷草转氨酶升高,谷丙转氨酶正常。头颅磁共振成像均示白质髓鞘化不良,例1还有丘脑对称性信号改变。全外显子二代测序发现,例1GLB1基因存在3p22.3(33137821-33138587)×1缺失突变,该片段缺失既往文献未见报道。结论婴儿型GM1神经节苷脂贮积症临床谱广泛。2例患儿均有皮肤异常,相对罕见。例1多发关节挛缩,尚未见文献报道,可能为新发表型。例1GLB1基因3p22.3(33137821-33138587)×1片段缺失为新突变,扩大了本病基因谱。     

庞贝病神经系统损伤的研究进展北大核心CSCD

庞贝病(Pompe disease)亦称糖原贮积病Ⅱ型,是常染色体隐性遗传的罕见病,随着酶替代疗法的应用,越来越多的庞贝病患者可存活至成年,以往未曾观察到的神经系统相关临床表现逐渐显现。神经系统受累严重影响庞贝病患者的生活质量,系统了解庞贝病神经系统损伤的病理变化、临床表现、影像学表现,对庞贝病的早期识别、早期干预有重要意义。该文就庞贝病神经系统损伤的研究进展进行综述。     

52例黏多糖病酶学分型及临床特点分析

目的：探讨黏多糖病（MPS）疾病谱及其临床特点。方法：对2009年1月至2011年12月75例高度疑似MPS患儿同时进行尿黏多糖（GAG）定量和电泳分析以及7种MPS酶学分析。采用荧光分析法分别检测白细胞α-L-艾杜糖酶、艾杜糖-2-硫酸酯酶、α-N-乙酰氨基葡糖苷酶、半乳糖胺-6-硫酸酯酶、β-半乳糖苷酶、芳基硫酸酯酶B及β-葡萄糖醛酸酶活性。结果：根据临床、放射学及酶学检查确诊MPS 52例,年龄4.0±2.2岁,其中I型5例（10%）,Ⅱ型20例（38%）,ⅣA型20例（38%）,Ⅵ型6例（12%）,Ⅶ型1例（2%）,未发现ⅢB、ⅣB型患儿。除2例ⅣA型患儿外,其余50例MPS 患儿尿GAG/Gr比值均较同龄儿增高。尿GAG定量增高者均确诊为MPS。绝大多数患儿于生后1~2岁起病,常伴有疝、心脏瓣膜病。Ⅰ、Ⅱ、Ⅵ 型患儿表现面容丑陋、皮肤粗糙、矮小、关节僵硬及活动受限,ⅣA型主要表现为矮小、骨骼畸形及关节松弛。结论：MPS Ⅱ型和ⅣA型是MPS最常见类型,其次是Ⅵ型及Ⅰ型。MPS患儿以特殊外貌为临床特点,包括面容丑陋、皮肤粗糙、矮小、骨骼畸形等。尿GAG定量测定可作为一种简便、快速、可靠的MPS筛查方法在临床上推广应用。     

Quantification of the iduronate-2-sulfatase activity in prenatal diagnosis of mucopolysaccharidosis type n北大核心CSCD

Objective To evaluate the activity of iduronate-2-sulfatase (IDS) in fetal villi and peripheral blood plasma of pregnant women at high risk of mucopolysaccharidosis type II (M P S II), a n d to discuss t h e application of gene analysis in prenatal diagnosis of MPS II. M e t h o d s The enzymatic testing and gene analysis results of 23 pregnant women at high risk of MPS II, who underwent prenatal diagnosis in Guangzhou Women and C h i l d r e n ' s Medical Center from February 2013 to December 2 0 2 0, w e r e analyzed retrospectively. The IDS activity in fetal villi (3 0 c a s e s) and plasma (2 8 c a s e s) was detected by artificial substrate fluorescence. The IDS activity in fetal villi (2 8 c a s e s) and plasma (3 4 c a s e s) of normal pregnant women was taken as control. M e a n w h i l e, the fetal villi of both pregnant women at high risk of MPS II and normal pregnant women were also analyzed by gene testing and for fetal sex identification. Data were compared between groups by t h e i n d e p e n d e n t samples t test. R e s u l t s The normal reference values of the IDS activity in fetal villi and plasma of normal pregnant women w e r e (7 1 . 2 ± 2 3 . 4) n m o l / (m g • 4 h) and (6 1 1 . 1 ± 1 1 4 . 5) n m o l / (m L * 4 h), respectively. Among the 30 cases of high-risk fetal v i l l i, the IDS activity in fetal villi of 8 affected male fetuses was (1 . 7 ± 0 . 3) n m o l / (mg • 4 h), which was significantly lower than that of 11 unaffected male fetuses (8 3 . 2 ± 6. 3) n m o l / (m g - 4 h) and that of 9 n o n - c a r r i e r female fetuses (8 0 . 0 ± 7. 5) n m o l / (m g - 4 h) (t = 10. 8, 8. 8; all P < 0. 0 1) . M e a n w h i l e, t h e IDS activity was m e a s u r e d in t h e m a t e r n a l p e r i p h e r a l p l a s m a of 28 p r e g n a n t women at high risk of MPS II • Among t h e m, t h e IDS activity in 8 affected male fetuses w a s (2 2 5 . 4 ± 2 0 . 5) n m o l / (m L • 4 h), w h i c h was significantly lower t h a n that in non-affected male fetuses[ (4 5 1 . 0 ± 1 5. 1) n m o l / (mL • 4 h) ] and that in n o n - c a r r i e r female fetuses[ (4 6 7 . 7 ± 4 5 . 3) n m o l / (m L • 4 h) ]. Eight known pathogenic mutations were found i n 3 0 c a s e s a t high risk of MPS II of fetal v i l l i, a n d the mutation types were c. 1048A > C, c. 2 1 2 G > A, c. 5 1 4 C > T, c. 2 5 7 C > T, C. 4 2 5 C > T, a n d C. 9 9 8 C > T . O f t h e 8 c a s e s, 6 affected male fetuses h a d significantly r e d u c e d IDS a c t i v i t i e s, and the other 2 female carriers had normal IDS enzyme activities. Conclusions The IDS activity in fetal villi and peripheral plasma of pregnant woman is consistent with the gene analysis results. The IDS activity has an important reference value for the prenatal diagnosis of MPS II in the first trimester. When no genetic mutations are found in the probands or the pathogenicity of the new mutation remains unclear,the IDS activity in fetal villi can be detected separately for the prenatal diagnosis of MPS H © 2019 Chinese Journal of Experimental Traditional Medical Formulae. All rights reserved.     

糖原贮积病Ⅱ型酶替代治疗1例报告

目的探讨晚发型糖原贮积病Ⅱ型(GSDⅡ)的临床特点及应用酶替代治疗的效果。方法回顾性分析1例确诊为GSDⅡ患儿的临床、实验室资料及基因检测结果,随访酶替代治疗效果并复习相关文献。结果患儿1岁以后逐渐出现肌无力的表现。肌酸激酶675~1 286 U/L,α-葡糖苷酶酶活力为12.0 nmol/(g·min);肌电图提示双下肢肌源性损害;二代测序检测发现GAA基因的复合杂合突变,均为微小变异;肌肉活检符合糖原累积病理特征。诊断GSDⅡ后给予人重组α-葡糖苷酶20 mg/kg,缓慢静脉滴注,每2周1次治疗1年,肌无力症状无明显加重。结论早期、足量的酶替代治疗是GSDⅡ唯一可能的治疗手段。     

黏多糖贮积症Ⅰ型二例基因突变检测及产前诊断

目的 对黏多糖贮积症Ⅰ型病例进行基因检测,对再孕母亲进行产前诊断.方法 用酶学检测方法 确诊2例黏多糖贮积症Ⅰ型先证者;采用PCR扩增技术结合序列分析的方法,检测2例先证者血液及其再孕母亲羊水细胞中IDUA基因外显子及其两侧内含子.结果 在2例经酶学检测确诊的先证者中共检测出4种基因突变:p.L238R、c.883InsC、c.531InsT、p.L346R,2种为插入突变,2种为错义突变.在先证者1母亲羊水细胞IDUA基因中未发现致病基因突变,羊水细胞中IDUA酶活性为9.0 nmol/(h·mg蛋白);在先证者2母亲羊水细胞IDUA基因中检测到与先证者相同的两个致病突变,羊水细胞中IDUA酶活性为0.5 mol/(h·mg蛋白).结论 从黏多糖贮积症Ⅰ型先证者发现的4种突变中,p.L346R为已知突变,p.L238R,c.883InsC,c.531InsT为首次发现的新突变.胎儿1未获得与先证者相同致病基因,为正常胎儿.胎儿2获得与先证者相同致病基因,为受累胎儿.产前基因诊断结果 与酶学产前诊断结果 相符合.

Abstract：

Objectiye Mucopolysaccharidosis type Ⅰ(MPS Ⅰ; MIM# 252800)is an autosomal recessive disease that results from the deficiency in the lysosomal enzyme α-L-iduronidase(IDUA).IDUA is one of the enzymes involved in degradation of glycosaminoglycans heparan sulphate and dermatan sulphate.The deficiency of IDUA leads to widespread accumulation of partially degraded mucopolysaccharides inside lysosomes,resulting in progressive cellular and multiorgan dysfunction. Up to now there is no definitely effective treatment for this disorder,therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis for the MPS Ⅰ families.This study was conducted to detect IDUA gene mutation in patients with MPS Ⅰ and make a definite diagnosis of homozygote or heterozygote and make first trimester prenatal diagnosis.Method The 2 male probands included in this study were diagnosed as MPS Ⅰ patients in Peking Union Medical College Hospital,case 1 was 2 years old and case 2 was 5 years old.Genomic DNA was extracted from leucocytes in the 2 patients and 2 mothers' cultured amniocytes.IDUA gene DNA sequence was amplified by polymerase chain reaction(PCR)and the PCR products were sequenced directly.Novel mutations were analyzed in 100 normal chromosomes.Result The genotype of case 1 was p.L238R/c.883InsC,while of case 2 was c.531InsT/p.L346R.The fetal case 1 did not inherit the same pathogenic inherited the same pathogenic mutations with the proband,the genotype of fetal 2 was c.531InsT/p.L346R,in 2 MPS Ⅰ patients,p.L238R,c.883InsC,c.531InsT were novel.The fetal case 1 was diagnosed as normal fetus while the fetus 2 was diagnosed as affected.The results of the two kinds of prenatal diagnostic methods were correspondent with each other.     

一家三同胞神经元蜡样质脂褐质沉积症7型及其MFSD8基因新突变北大核心CSCD

目的神经元蜡样质脂褐质沉积症（neuronal ceroid lipofuscinosis,CLN）为一类严重的溶酶体贮积症,神经变性病,本研究拟通过对罕见的一家CLN7型三同胞的临床经过及其基因突变分析,对本症进行探讨。方法先证者,女,5岁时因“间断抽搐伴智力运动发育倒退2．5年”于2015年12月就诊,通过临床调查、头颅磁共振成像（MRI）扫描、生化代谢及基因分析进行病因诊断。结果先证者于2岁6个月起病,出现抽搐发作,伴智力运动倒退及视力下降,进行性加重。头颅MRI扫描显示弥散性脑萎缩,血液氨基酸、酯酰肉碱谱分析及尿有机酸分析未见异常,外周血白细胞棕榈酰蛋白硫脂酶、三肽酰肽酶活性正常,MFSD8基因存在c．1351-1G〉A和c．300T〉G2个致病突变,父母各携带1个突变,均为未报道的新突变,证实为CLN7型。患儿同胞哥哥临床经过与患儿相似,7岁时死于严重脑病,病因不明。弟弟2岁后出现运动障碍,4岁起出现抽搐,其MFSD8基因存在与先证者相同的c．1351-1G〉A和c．300T〉G2个致病突变,亦为CLN7型患者。结论CLN7型属于CLN的罕见类型,本研究一家三同胞诊断过程曲折,经基因分析确诊,并发现了MFSD8基因2个新突变。对于本病目前尚无有效的药物治疗方法,预后不良,在明确基因诊断基础上,对下一个同胞进行产前诊断是预防家族中疾病再发的关键。     

高危儿早期筛查与干预北大核心CSCD

通过近年来国内外相关文献的查阅,结合我国高危儿医疗诊治的循证依据,在参加编写我国首部《中国儿童脑瘫康复指南》的是础上,围绕高危儿的概念、高危儿的评定、高危儿的干预及高危儿的随访管理进行探讨,以期提高我国各级医院的医护人员对高危儿的规范化筛查、干预及随访管理。     

造血干细胞移植治疗黏多糖病研究进展

黏多糖病(MPS)是一种由于溶酶体中一些酶的缺陷使酸性黏多糖在体内不能完全降解而贮积在各种组织中引起的一组疾病,最终因心血管和肺功能衰竭而死亡.酶替代疗法是其治疗措施之一,但有其局限性;异基因造血干细胞移植是另一种措施.MPS Ⅰ型和Ⅵ型移植效果确定.移植最佳年龄是18个月.首选人类白细胞抗原全相合无病同胞,非血缘脐血是无合适同胞的优先选择.移植后3个月,酶活性可增加至预期值.移植后,肝、脾和心脏有改进,髋骨和脊柱畸形、角膜混浊和听力有改善.但骨生长和重建恢复差,视网膜退化和心脏瓣膜增厚继续进展.认知能力的恢复随移植时年龄的不同而异.通过移植,患者生存率达50%～85%.白消安和环磷酰胺预处理和诊断、移植间隔期比较短,故而能够提高患者生存率.     

川崎病流行病学研究进展北大核心CSCD

川崎病是一种主要发生于<5岁儿童的系统性血管炎,自40多年前首次在日本被报道以来,全世界已有超过60个国家报道了川崎病的发生,已成为发达国家后天性儿童心脏病的主要原因。不同的调查方法、依赖于临床表现的诊断和不完全川崎病病例的比例导致各国流行病学结果存在差异性和局限性,高估或低估了真实发病率。但流行病学研究揭示了该病病因与基因及环境等因素密切相关的特点,包括亚裔人口的高发病率、家族内高发病率、显著季节性和年龄分布等。疾病本身发病率的增高、临床工作者对疾病认识的增强及就诊率的提高或许共同导致近年来该病发病率在多数国家呈上升趋势。该文对各国的川崎病流行病学研究进行回顾。