Oculo-facio-cardio-dental syndrome caused by BCOR gene mutations: a case report北大核心CSCD

患儿女,足月儿,生后5h,因胎儿期发现心脏畸形,生后发绀1次入院。检查发现存在眼、面部、四肢、心脏多发畸形,全外显子基因检测显示BCOR基因存在致病性杂合突变c.2428C>T(p.Arg810^(*)),该患儿诊断为眼-面-心-牙综合征。住院期间予以辅助通气改善氧合、营养支持等治疗,生后1个月于外院行右室双出口矫治术,眼部病变于眼科随诊择期手术治疗。对于存在眼、面部、心脏多发畸形的新生儿应注意眼-面-心-牙综合征可能,需尽早完善基因检测明确诊断,同时积极给予眼及心血管方面的对症治疗,有助于改善患儿预后。     

MSTO1基因变异致线粒体肌病伴共济失调一家系病例报告并文献复习

对2019年10月来中南大学湘雅医院就诊的MSTO1基因变异致线粒体肌病伴共济失调一个家系的临床特征和基因变异特点进行回顾性分析。先证者, 女, 11岁, 1岁6个月发现运动和语言发育迟缓, 构音障碍。弟弟, 9岁, 1岁3个月出现类似症状。先证者及弟弟均有肌肉无力与共济失调, 其头部磁共振成像均示小脑萎缩。二者肌电图均提示神经源性改变。基因检测发现MSTO1复合杂合突变:c.1259delG;p.G420VfsX2和c.571 C>T;p.R191X, 分别遗传自其父母, 弟弟有同样位点突变。予"鸡尾酒疗法", 2周后患儿症状开始改善, 语言及运动较前进步。     

Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review北大核心CSCD

目的 总结SYNGAP1基因相关常染色体显性智力障碍5型患儿临床表型及遗传学特点。方法 回顾性分析中南大学湘雅医院儿科诊治的8例SYNGAP1基因相关智力障碍患儿的临床资料。结果 8例患儿的平均起病年龄为9月龄,均伴有中重度发育迟缓(语言落后为著),其中7例患儿伴癫痫发作。8例患儿中7例为新发杂合变异(3例移码变异、2例无义变异和2例错义变异),1例为6p21.3微缺失。目前已报道的中国SYNGAP1基因变异相关智力障碍患儿(包括该研究)有48例,其中40例伴癫痫发作,癫痫发作平均起病年龄为31.4月龄,多为移码变异(15/48,31%)和无义变异(19/48,40%)。治疗上,有癫痫用药史记录的33例患儿中,丙戊酸抗癫痫发作治疗对多数患儿有效(85%,28/33),其中48%(16/33)患儿丙戊酸单药或联合用药治疗达到发作完全控制。结论 SYNGAP1基因相关常染色体显性智力障碍5型患儿起病年龄早,多数患儿伴癫痫发作,以移码变异和无义变异为主,丙戊酸抗癫痫发作治疗对多数患儿有效。     

Treatment of Gorham-Stout disease with zoledronic acid and interferon-α: a case report and literature review

Gorham-Stout disease is a rare disease characterized by osteolysis, angiomatosis, and soft-tissue swelling. It is a diagnosis of exclusion and has an unknown etiology. Chylothorax is a common complication of the disease that is associated with a high mortality rate. There is no standard of treatment. We report a case of a 16-year-old female with Gorham-Stout disease and recurrent pleural effusions who was successfully treated with concurrent zoledronic acid and peg-interferon α-2b.     

Mucopolysaccharidosis Ⅶ:report of a case and renew of the literature

objective To investigate the clinical characteristics and diagnosis of mucopolysaccharidosis Ⅶ. Method The clinical and biochemical features of an infant with mucopolysaccharidosis Ⅶ confirmed by enzyme assay were analyzed.Result The 2 month-old male infant showed hydrops fetalis,mental retardation,coarse face,corneal clouding,hepatosplenomegaly,hernias,Alder-Reilly granules in the leucocytes and decreased platelet(32×109/L).The biochemical markers showed urinary glycosaminoglycans(GAG)(532.8 mg/L,controls＜70.0 mg/L).The ratio of GAG/creatinine was 161.3(controls:26.2±11.7).Serum chitotriosidase activity was 315.8 nmol/(ml·h) [control ＜53 mol/(ml·h)].Beta-glucuronidase activity was deficient in isolated leukocytes.Conclusion Severe form of mucopolysaecharidosis Ⅶ exhibited characteristics of hydrops fetalis.hepatosplenomegaly, coarse face,thromboeytopenia and Alder-Reilly granules in the leucocytes.The measurements of GAG in urinary and beta glucuronidase in leucocytes are critical to diagnosis and deferential diagnosis.     

Detection of RAS gene mutation and its clinical significance in children with acute lymphoblastic leukemia北大核心CSCD

Objective To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia. Methods A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children. Results Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×109/L at diagnosis was worse (P<0.05). Conclusions RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis. © 2022 Xiangya Hospital of CSU. All rights reserved.     

Holocarboxylase synthetase deficiency induced by HLCS gene mutations: a rare disease study北大核心CSCD

男性患儿,16月龄,因发现头面部红斑15个月,外阴红斑10个月,加重5 d就诊。患儿新生儿期即出现口周、眼周红斑,婴儿期出现颈部、腋下、外阴三角区等腔口和皱褶部位的红斑、丘疹,可见脱屑和糜烂。血气分析提示代谢性酸中毒,血遗传代谢病氨基酸和酰基肉碱谱分析、尿液有机酸分析结果均提示多种羧化酶缺乏症,基因检测结果提示HLCS基因存在c.1522C>T(p.R508W)纯合突变。最终该患儿诊断为全羧化酶合成酶缺乏症,口服生物素治疗取得良好的临床疗效。该文总结了1例全羧化酶合成酶缺乏症患儿的临床资料,对其病因、诊断、治疗进行归纳总结,为临床医生诊断该类罕见疾病提供思路。     

In Utero diagnosis and management of a fetus with homozygous α-Thalassemia in the second trimester: a case report and literature review

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous α-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted.     

Steroid-resistant nephrotic syndrome associated with steroid sulfatase deficiency—x-linked recessive ichthyosis: a case report and review of literature

Nephrotic syndrome associated with X-linked recessive ichthyosis due to steroid sulfatase deficiency has rarely been reported in English literature. We describe a 4 and a half-year-old boy presenting with steroid-resistant nephrotic syndrome (SRNS) with an underlying ichthyotic skin present since birth. Renal biopsy revealed minimal change disease. As many of the male members of the family also showed similar skin manifestations, genetic analysis was done on the patient, which revealed deletion of the steroid sulfatase (STS) gene spanning both the 3′ as well as the 5′ends. The patient was thus diagnosed with SRNS associated with X-linked recessive ichthyosis. He was started on cyclosporine regimen, and remission was achieved in 5 weeks. We speculate that the deficiency of STS resulting in increased cholesterol sulfate accumulation interferes with the integrity of adherens junctions present between glomerular epithelial cells of the slit diaphragm, and this results in proteinuria and nephrotic syndrome. The nephrotic syndrome remitted with a calcineurin inhibitor medication. Conclusion: We suggest that the deficiency of STS is another one in an increasing list of genetic causes of podocytopathy and nephrotic syndrome. Remission of proteinuria in such a case may be achieved with immunosuppressive medication.     

Congenital brachioesophagus with secondary intrathoracic stomach associated with rachischisis described as “serpentine-like syndrome”: a case report and literature review

We report a male infant with severe brachioesophagus with intrathoracic stomach, duodenum, pancreas, and spleen associated with short neck because of rachischisis and scoliosis, an extremely rare condition described recently as “serpentine-like syndrome”. Our case died and we review four similar cases reported in the English literature.     

Slide laryngotracheoplasty for treating congenital subglottic stenosis: a case report and follow - up北大核心CSCD

对2021年12月山东大学附属儿童医院呼吸介入科收治的1例先天性声门下区狭窄(C-SGS)行滑动喉气管成形术患儿资料进行回顾性分析。患儿,女,2个月15 d,因呼吸困难2个月余,气管切开术后23 d就诊。支气管镜、环状软骨B超提示声门下区狭窄,未见瘢痕增生。结合患儿病史,诊断为C-SGS。入院后2周行滑动喉气管成形术,术后即拔除气管切开套管。术后2个月余随访,恢复良好,无呼吸困难表现。提示对于C-SGS,可在明确诊断后早期、安全手术,提供即时和足够的气道空间,保证良好的声音质量和吞咽功能。     

Transient hepatitis B surface antigen circulation after Infanrix-Hexa®: a case report and review of the literature

The authors describe the case of a 70-day-old boy who was mistakenly diagnosed as suffering from acute hepatitis B, when he presented with persistent unconjugated hyperbilirubinemia and transaminasemia and was found to be seropositive for the hepatitis B surface antigen. The antigenemia was transient and related to his recent immunization with Infanrix-Hexa®. Caution is required during interpretation of a positive HBsAg test that is obtained within 28 days after vaccination against hepatitis B.     

Case report of unrelated cord blood transplantation for the treatment of recurrent refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with intestinal perforation and literature review北大核心CSCD

目的探讨非血缘脐带血移植(UCBT)治疗儿童复发难治性EB病毒相关噬血细胞综合征(EBV-HLH)的临床经验及疗效。方法回顾性分析2015年9月郑州大学第一附属医院儿科诊治的1例复发难治性EBV-HLH合并肠穿孔,最终接受UCBT治愈患儿的临床资料,并进行文献复习。结果患儿,男,1岁6个月,因发热15 d,皮疹9 d为主诉入院,主要表现为高热,肝、脾、淋巴结大,快速进展的全血细胞减少、肝功能损害,骨髓涂片可见吞噬血细胞,2015年9月确诊为EBV-HLH,按国际组织细胞协会制定的HLH-2004方案化疗,维持期间2次复发,给予挽救性二线方案培门冬酰胺酶、阿霉素脂质体、依托泊苷、甲泼尼龙(L-DEP方案)化疗,化疗后评估噬血细胞综合征指标完全缓解,突发肠穿孔,紧急外科手术行小肠造瘘术,病情稳定后,给予氟达拉滨+白消安+环磷酰胺方案(Flu+BU+CY方案)预处理后行UCBT,全程静脉营养支持,移植后第13天中性粒细胞植入,第35天血小板植入,嵌合率为100%,植入成功;移植后第15天出现肝小静脉闭塞征,移植后第22天出现真菌性肺炎,移植后第26天出现皮肤移植物抗宿主病(GVHD)Ⅱ度,给予相应治疗好转;移植后第49天行二期肠造瘘关瘘术;现随访至移植后70个月,患儿一般状况良好,病情持续缓解,无慢性GVHD及其他合并症。结论异基因造血干细胞移植可能是治疗儿童复发难治性EBV-HLH的唯一有效手段;无合适同胞或非血缘供者时,非血缘脐带血干细胞可作为移植物来源;肠穿孔术后肠造瘘不是移植禁忌。     

Stenosing ureteritis in a 7-year-old boy with Henoch–Schönlein purpura nephritis: A case report and review of the literature

IntroductionUrinary tract obstruction resulting from Henoch–Schönlein purpura (HSP) is an extremely rare urologic entity. If the genitourinary system is involved, it is primarily in the form of a focal proliferative glomerulonephritis. Stenosing disease has received little attention in the literature and treatment options are limited. Despite early intervention renal loss may be inevitable.Case reportA 7-year-old African American male presented with renal failure secondary to bilateral sclerosing ureteritis 1 month after initial presentation with HSP. There was significant disease progression and he required multiple procedures, ultimately bilateral ureterocalycostomies and a left nephrectomy.DiscussionHSP is an immune-mediated necrotizing vasculitis. It can affect any organ system; however, in the genitourinary system, focal proliferative glomerulonephritis is a common manifestation, occurring in 20–90% of cases [8]. Extrarenal manifestations are rare.ConclusionUreteritis and obstruction may be late occurrences, but should be considered in all patients presenting with a history of HSP and new-onset flank pain, acute renal failure, or anuria. Families and patients should be counseled that renal impairment may be a consequence of stenosing ureteritis. Management of these patients can be complicated but surgical correction must be considered in the treatment algorithm once the disease has stabilized.     

Association of ventricular septal defect with rare variations of the HAND2 gene北大核心CSCD

目的对室间隔缺损(ventricular septal defect,VSD)与HAND2基因启动子区罕见变异的关联性进行分析,并对相关分子机制进行初步探索。方法收集349例VSD组患儿和345例健康对照组儿童血液样本,通过聚合酶链反应扩增目的片段并进行测序,确定HAND2基因启动子区的罕见变异位点。使用双荧光素酶检测进行变异位点功能分析,并通过电泳迁移率变动分析进行分子机制研究,同时使用TRANSFAC和JASPAR数据库预测转录因子。结果通过测序发现3个变异位点(g.173530852A>G、g.173531173A>G和g.173531213C>G)只出现在10例VSD患儿的HAND2基因启动子上,其中4例患儿仅有1个变异位点。双荧光素酶检测显示g.173531213C>G降低了HAND2基因启动子转录活性。电泳迁移率变动分析和转录因子预测提示g.173531213C>G产生了1个转录因子结合位点。结论HAND2基因启动子区的罕见变异g.173531213C>G可能通过影响转录因子的结合,进而参与VSD的发生发展。     

Metachronous Wilms tumor associated with pulmonary embolism: how can we detect these cases early? A case report and literature review

A 4-year-old girl developed right metachronous Wilms tumor 2 years after completing treatment for a left-sided stage I Wilms tumor. The original treatment included 7 weeks of chemotherapy, delayed nephrectomy, and another 3 weeks of chemotherapy. The metachronous tumor on the right side extended into the inferior vena cava and right atrium. She developed pulmonary embolism as a result. She received chemotherapy and developed liquifaction of the tumor and toxic shock. She also had surgery. The patient is alive 3 years after the original diagnosis and 10 months after the relapse. The authors report this unusual case and discuss whether these cases can be identified early.     

Is there a role for high dose chemotherapy and blood stem cell rescue in childhood hepatoblastoma presenting with lung metastases? A case report and literature review

We report the use of high dose chemotherapy with peripheral blood stem cell rescue as a consolidation treatment for a 3-year-old child affected by metastatic hepatoblastoma, who achieved complete lung response only after conventional treatment. The patient is presently alive 27 months after high dose chemotherapy with blood stem cell rescue with no evidence of disease.The role of high dose chemotherapy with blood stem cell rescue to consolidate the complete clearing of lung disease in metastatic hepatoblastoma remains controversial; the data available in the literature and our experience seems to suggest to keep this treatment option open to further consideration in the clinical setting of high-risk patients.     

Short-term persistent symptoms in preschool children with mild/common coronavirus disease 2019 caused by Omicron variant infection after discharge: a follow-up study北大核心CSCD

目的探讨学龄前儿童感染严重急性呼吸综合征冠状病毒-2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)Omicron变异株后的相关持续症状,为制订感染后的随访计划,减少和预防患儿感染后的相关症状提供依据。方法以2022年4月13日—5月8日由上海市仁济医院南院儿科病房出院的0~5岁Omicron BA.2感染的患儿为研究对象,收集人口学及临床资料,并以连续2次、间隔时间超过24 h的SARS-CoV-2核酸转阴时间为随访起点,其转阴后的4~5周为随访截点,对主要带养人进行电话随访,了解患儿出院后相关持续症状。结果符合纳入条件的103例患儿中,男孩61例,女孩42例,中位年龄为18个月。主要带养家长已接种2针及以上新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫苗的比例为64.1%(66/103)。患儿最常见的症状为发热(98.1%,101/103),其次是咳嗽/咳痰(63.1%,65/103)、胃肠道问题(37.9%,39/103)、食欲下降(30.1%,31/103)、乏力(27.2%,28/103)、鼻塞/流涕(16.5%,17/103)等。出院1个月时随访报告44例(42.7%)至少有1种持续症状,包括呼吸道相关症状(14例,13.6%)、胃肠道问题(19例,18.4%)等。主要带养人接种2针及以上COVID-19疫苗的患儿SARS-CoV-2核酸转阴时间较家长未接种或接种1针的患儿核酸转阴时间缩短(P<0.05),但2组患儿存在至少1种持续症状的比例差异无统计学意义(P>0.05)。结论近半数SARSCoV-2 Omicron变异株感染学龄前儿童出院后存在持续相关症状,多为胃肠道症状和呼吸道症状,但大部分症状轻微,需持续随访关注其转归情况。主要带养人COVID-19疫苗接种对儿童可起到一定的保护作用。     

Severe psychomotor and metabolic damages caused by a mutant thyroid hormone receptor alpha 1 in mice: can patients with a similar mutation be found and treated?

Individuals suffering from the resistance to thyroid hormone syndrome (RTH) have a mutation in thyroid hormone receptor (TR) beta. Surprisingly, no patient with a mutation in TRalpha1 has been found. To facilitate their identification, animal models with a RTH-like mutation in TRalpha1 have been generated. The mutations introduced into the mouse decrease affinity to ligand, resulting in a 'receptor-mediated hypothyroidism' in tissues expressing the mutant receptor: brain, heart and bone. The mice present minor perturbances in thyroid hormone homeostasis, but show major aberrancies in postnatal development, psychomotor behaviour and metabolism. These parameters are akin to those seen in endemic cretinism and untreated congenital hypothyroidism. Treatment of the mice with high doses of triiodothyronine leads to normalization or amelioration of the dysfunctions when applied at adequate developmental periods. CONCLUSION: Our studies on mice suggest the existence of a potentially debilitating disease caused by a mutant TRalpha1, and provide insights for identification and treatment of corresponding patients.