儿童脱屑性间质性肺炎1 例报告并文献复习

目的探讨儿童脱屑性间质性肺炎(DIP)的病因、临床特点、诊治及预后。方法回顾分析1例按临床-放射-病理(C-R-P)模式确诊的DIP患儿的临床资料,并以desquamative interstitial pneumonia与child 、脱屑性间质性肺炎与儿童为检索词,在PubMed、万方数据库检索截止至2019年7月的相关文献。结果 4岁男童,咳嗽1个月,伴气促,肺部中、细湿啰音,杵状指;肺CT示毛玻璃样影和网格影。患儿抗感染治疗临床无好转,行胸腔镜下右肺组织活检术,肺组织病理符合DIP。随之患儿采用激素治疗,随访44个月,症状消失、病灶基本吸收。文献检索到国内病例11例、国外病例42例,除外临床资料不完整者,最终筛选获得30例,加上本例患儿共31例,其中男14例、女13例,4例资料中未提及,年龄从新生儿～13岁。病因主要为先天性表面活性物质代谢缺陷,其他包括特发性、吸入二手烟、药物以及全身性疾病。临床表现主要为呼吸困难和干咳,肺部影像学以毛玻璃影为主,肺功能主要为限制性通气障碍。治疗主要采用糖皮质激素和免疫抑制剂。结论儿童DIP较为少见,病因和发病机制与成人有显著差别,应尽早肺活检病理检查以确诊,激素和/或免疫抑制剂为一线治疗药物。     

儿童原发性乳糜性心包积液１例报告并文献复习

目的探讨儿童原发性乳糜性心包积液的临床特点及诊治。方法回顾分析1例确诊儿童原发性乳糜性心包积液患儿的临床资料,并以children primary chylopericardium、pediatric primary chylopericardium、儿童原发性乳糜性心包积液为关键词,在万方数据知识服务平台、中国知网、PubMed数据库中检索,收集并分析已报道的国内外儿童原发性乳糜性心包积液病例。结果患儿,女,3岁11月龄,咳嗽、胸闷、胸痛、呼吸困难;心脏浊音界扩大,心音遥远,心律齐,未闻及心脏杂音。胸片示心影外形增大。彩色多普勒超声心动图示中大量心包积液。心包穿刺引流出乳糜样液体。经过对症支持治疗,患儿病情好转,但心包腔内仍有积液。随访1年余,心包积液量逐渐减少,患儿无特殊不适。结论原发性乳糜性心包积液在儿童中罕见,发生不明原因呼吸困难和心音低钝时需警惕,确诊需要行心包穿刺术。     

反复发热伴MEFV基因突变患儿10例临床分析及文献复习

目的　探讨在非高危人群中家族性地中海热（FMF）的诊断要点及其临床表现与基因型的关系。方法　回顾性分析重庆医科大学附属儿童医院2016-07-27—2017-11-15收治的10例反复发热伴MEFV基因突变患儿的基因检测报告及临床表现,结合国内外FMF相关文献,对诊断要点及其临床表现与基因型进行总结归纳。结果　10例患儿中共发现4个MEFV基因突变,分别为G304R、E148Q、P369S、R408Q,其中纯合突变4例（40.0%）,杂合突变2例（20.0%）,复杂突变4例（40.0%）。10例患儿中9例有反复发热,1例有反复化脓性扁桃体炎。该10例患儿根据Tel Hashomer标准,有1例患儿疑似诊断FMF,有8例患儿临床怀疑FMF;若根据Turkish儿科标准,则有7例患儿可临床诊断FMF。结论　FMF主要依靠临床诊断,可以通过基因检测来支持但不一定排除。携带M694V纯合型突变的FMF患者比其他突变的患者起病年龄更早,临床表现很可能更严重;而E148Q的致病性存在争议,其作为惟一突变时不支持FMF诊断。中国儿童中FMF发病率可能被低估,尚需纳入更多的研究对象,进一步研究。     

Nicolaides-Baraitser 综合征1 例报告并文献复习

目的探讨Nicolaides-Baraitser综合征的临床和基因突变特点。方法回顾分析1例Nicolaides-Baraitser综合征患儿的临床资料,并复习相关文献。结果男性患儿,2岁。1岁2个月起病,病初表现为双眼凝视、反应减低,无明显四肢抖动,持续时间数十秒后缓解,发作后疲惫入睡,间歇期如常,间隔10天左右发作1次,予卡马西平口服无效。1个月前出现全身快速抖动,有时伴发作性全身无力,数秒钟缓解,但发作频繁。患儿头围44 cm,特殊面容,三角脸、人中宽且长、上唇薄而下唇增厚、头部毛发少,右手通贯掌,步态正常;盖泽尔智力量表发育商57。脑电图示背景节律慢化,枕、颞区尖波、尖慢波大量发放,广泛性棘慢波多量发放,全导棘慢波爆发伴肌阵挛发作,监测到右侧枕区及颞区起源的局灶性发作各1次。基因检测发现患儿9号染色体SMARCA2基因c.3293(exon24)GA新生突变。文献检索国外共报道75例,其中61例有基因检测,2例为框内缺失突变、59例为错义突变。结论患儿为国内首次报道的Nicolaides-Baraitser综合征。     

AVPR2 基因变异致先天性肾性尿崩症2 例报告并文献复习

目的探讨先天性肾性尿崩症的临床特点、基因诊断及治疗。方法回顾分析2例先天性肾性尿崩症患儿的临床资料。结果 2例男性患儿分别为5岁和3岁2个月,均以多饮多尿、生长迟缓为主要表现。经禁水-加压素试验证实为持续低比重尿。尿崩症相关基因检测发现,例1患儿精氨酸加压素受体2(AVPR2)基因外显子2杂合错义突变c.650CT(p.P217L),且为新发变异。例2患儿AVPR2基因外显子1及外显子2缺失,亦为新发变异,其母亲为携带者,父亲AVPR2基因未见异常变异。对新发的变异位点通过Mutation-taster及Polyphen2软件预测为致病性变异。2例患儿口服氢氯噻嗪联合吲哚美辛治疗1年,尿量及夜尿减少,无电解质紊乱及肾功能受损等。结论 AVPR2基因为先天性肾性尿崩症的主要致病基因,发现2种国内外未见报道的新变异位点。     

低钾血症致肾囊性病变2 例报告并文献复习

目的探讨低钾血症导致的获得性肾囊性病变的临床特点和发病机制。方法总结2例以慢性低钾血症为主要表现、伴有肾囊性病变的肾小管疾病患儿的临床资料,并结合文献进行复习。结果 2例患儿均为男性,年龄分别为16岁和14岁,例1原发病为Dent病(1型)、例2为肾小管酸中毒(1型),共同特点为长期低钾血症史,未正规治疗、随访,均合并多发肾脏囊肿,无其他遗传性肾囊性病变的证据,例1合并肾功能异常、例2合并肾钙化。结论长期低钾血症可导致肾囊性病变,早期诊治、治疗和规律随访尤为重要。     

AKT3 基因相关巨脑畸形1 例报告并文献复习

目的探讨AKT3基因相关巨脑畸形(MEG)的临床特征。方法回顾分析1例AKT3基因相关MEG患儿的临床资料,并复习相关文献。结果女性患儿,4月龄,出生时无异常,出生胎龄39~(+4)周,体质量3 120 g,头围37 cm。出生后头围随月龄进行性增大,前额、后枕部突出,发育迟缓,四肢肌张力偏低,脊柱、四肢未见畸形。Gesell发育量表评估总发育商69。血生化、串联质谱、尿有机酸检查未见异常。头颅磁共振成像示双侧大脑半球脑白质量偏少,皮层信号相对未见异常,双侧侧脑室稍扩大。脑部血管成像未见明显异常。脑电图示正常婴儿脑电图。染色体核型分析未见异常。全外显子测序检测发现患儿AKT3基因存在c.1393CT(p.Arg465Trp)杂合变异。根据美国ACMG变异分类指南,考虑该变异为"2类-可能致病",提示患儿存在AKT3基因相关MEG。查阅文献,上述变异已在国外多个MEG患者中被报道过,国内尚未见报道。结论 MEG主要特征为头围增大,伴不同程度发育迟缓,可伴癫痫发作、孤独症等,部分存在多小脑回畸形、局灶性皮层发育不良,其临床表型谱复杂,基因测序有助于明确诊断。     

Familial Mediterranean fever gene mutations in the inner northern region of Turkey and genotype–phenotype correlation in children

Aim:   Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterised by recurrent episodes of fever, polyserositis and rash. The aim of this study was to determine the most common mutations and clinical features, and their relationships.
Methods:   The medical records of 78 patients were evaluated retrospectively. All of the patients had been diagnosed with FMF according to Tel Hashomer criteria between January 2005 and May 2008 in general paediatric clinics of the School of Medicine at Gaziosmanpasa University. Twelve mutations were detected in the 78 patients by polymerase chain reaction–enzyme-linked immunosorbent assay. The patients were classified into three groups according to allele status.
Results:   The most prominent clinical symptoms were abdominal pain (95%), fever (90%), arthritis (33%) and pleuritis (31%). Seventeen different genotypes were identified. The mutations were homozygous in 25 (32%) patients, compound heterozygous in 28 (36%) patients and heterozygous in 22 (28%) patients. No mutation was detected in three (4%) patients. The most frequent mutations were M694V (55%), M680I (16%), E148Q (10%) and P369S (4%). The mean symptom severity score was highest in the homozygous group, and high levels of C-reactive protein were also detected in this group.
Conclusions:   In addition to clinical criteria, molecular studies for detecting disease-causing mutations are needed to establish the diagnosis of FMF. FMF patients who were homozygous for MEFV gene mutations had a higher symptom severity score and higher incidence of appendectomy. The broad spectrum of mutations may reflect intercultural interactions of ethnic groups in Anatolia. Nation-wide studies may help to determine the relationships among demographic, clinical and genetic features of FMF.     

儿童Bainbridge-Ropers综合征1例报告并文献复习

目的探讨Bainbridge-Ropers综合征的临床特点。方法回顾分析1例Bainbridge-Ropers综合征患儿的临床资料及基因检测结果,并复习相关文献。结果女性患儿,11个月,表现为喂养困难,生长障碍,发育迟缓,特殊面容(小头畸形、弓形眉、睑裂上斜、鼻孔前倾、低位耳),尺偏手,四肢肌张力偏低。基因检测发现ASXL3基因存在新发杂合无义突变,为c.3106(外显子12)CT,导致蛋白质改变为p.(Arg1036*)。结论基因检测有助于Bainbridge-Ropers综合征的早期诊断。     

泛酸激酶相关神经变性病2 例报告并文献复习

目的探讨泛酸激酶相关神经变性病(PKAN)的临床特征及遗传学特点。方法总结分析2例PKAN患儿的临床资料及基因检测结果,并以Hallervorden-Spalz、脑组织铁沉积、NBIA和PKAN、PANK2为检索词,检索2019年3月前的PubMed、人类基因组突变数据库(HGMD)、中国知网数据库(CNKI)和万方数据库,进行文献复习。结果 2例患儿均为男性。例1患儿为7 岁2月龄,肌张力升高3年余,加重2周;头颅磁共振成像示苍白球病变;全外显子基因检测发现PANK2基因杂合变异C.515-527del、C.644-645delGAinsAT,其母亲携带杂合致病变异,父亲携带可疑杂合致病变异。例2患儿为14岁9月龄,走路不稳8年、加重1年;全外显子基因检测发现PANK2基因纯合变异c.397AG(p.Met133Val),其母亲为杂合变异,父亲未检测到变异。结论杂合和纯合PANK2基因变异均可导致发病。     

Familial Mediterranean fever in a childhood population in eastern Turkey

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of inflammation of serosal membranes. Amyloidosis is the most severe complication of the disease The aim of this study was to explore the magnitude of the FMF problem and to describe clinical phenotypic and genotypic profile in the childhood population in Eastern Turkey. METHODS: In this study, 52 patients who were diagnosed as FMF between January 2000 and January 2003 in Department of Pediatrics, Ataturk University Hospital, were included. The diagnosis of FMF was based on typical clinical and laboratory features. The 12 FMF mutations were investigated in the patients. RESULTS: Of the 52 patients, 30 (57.7%) were girls, 22 (42.3%) were boys, and the age ranged from 9 months to 15 years (8.5 +/- 3.2 years). A positive family history for FMF was noted in 33 (63.5%) patients. The mean onset age was 6 +/- 3.4 (from 8 months to 14 years). Nineteen children (36.5%) were symptomatic below the age of 5 years. Abdominal pain was observed in 50 (96.2%), fever in 42 (80.8%), arthralgia in 29 (55.8%), arthritis in 18 (34.6%), splenomegaly in 11 (21.2), hepatomegaly in 15 (28.8%), myalgia in 11 (26.2%), erysipelas-like erythema in 10 (19.2%), thoracic pain in four (7.7%), protracted febrile myalgia in three (5.8%), and seizures in two (3.8%). The most frequent mutation was the M694V/M694V. Clinical presentation of the patients was not different in respect with genotypes (P > 0.05). Two patients had chronic renal disease suggestive of amyloidosis. CONCLUSION: It was noted that the FMF patients in this study had a broad spectrum of mutation combination, which might reflect the intercultural interactions of ancient ethnic groups that lived in Anatolia, and these mutations were not significantly different in respect to clinical presentations.     

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??Objective To assess the efficiency of colchicine therapy in the treatment of Chinese pediatric patients with familial Mediterranean fever??FMF??. Methods In the prospective trial??pediatric patients with proven FMF??either by Tel Hashomer criteria or by MEFV gene testing??received colchicine treatment. The following indexes and results were recorded??including the clinical manifestations and signs??CRP??ESR??MEFV sequencing results of pathogenic genes??and the dosage??effective rate and follow-up of colchicine treatment. Results Twelve children??10 diagnosed by Tel Hashomer criteria vs. 2 by MEFV sequencing?? were enrolled in the study??with the median age at diagnosis/initiation of colchicine of 8??1??10?? years. They received colchicine treatment at the dose of 0.01??0.025 mg/??kg·d??. Among them 11 completed the study??while 1??8.3%?? had anaphylaxis and quit. During a median follow-up of 11??8??38?? months??the response rate was 100%. Conclusion??Colchicine is effective in Chinese children patients with FMF??which should be given as earlier as possible to prevent the consequent damage caused by chronic inflammation.