Idiopathic infantile arterial calcification in a 12-year-old girl presenting as chronic mesenteric ischemia: imaging findings and angioplasty results

We report an unusual case of chronic mesenteric ischemia presenting in a 12-year-old girl with idiopathic infantile arterial calcinosis (IIAC). This is the first reported case in the literature of chronic mesenteric ischemia in the setting of IIAC. The girl presented with a classical history of postprandial abdominal pain. Imaging demonstrated significant stenoses of the celiac axis, superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). Angioplasty of the celiac axis and SMA was attempted, with successful dilation of the SMA only. At 3-, 6- and 12-month follow-ups, the child’s symptoms had almost resolved. This case report has three important ramifications: chronic mesenteric ischemia is a possible clinical presentation in children with IACC, pre-angioplasty imaging is important in guiding treatment approach, and angioplasty was effective in this case of chronic mesenteric ischemia and offers hope for other similarly affected children.     

儿童型脊髓性肌萎缩症的临床与病理研究

目的：总结42例儿童型(I～III型)脊髓性肌萎缩症(SMA)的临床与病理特征,以探讨儿童型SMA临床与病理学特征及其意义。方法：收集42例做过肌活检的SMA I～III型病例,进行临床、肌肉病理学(常规组织学及组织化学方法)分析。结果：不同型SMA临床各有特点,主要是病情轻重和起病年龄有关。起病越早者,病情越重。肌活检显示SMA I型为大组分布的圆形萎缩肌纤维,而非角形纤维,呈不完全同型肌群化,常累及整个肌束;SMA II型少见大组萎缩肌纤维,同型肌群化突出;SMA III型病理变化多样,以同型肌群化为主。结论：临床表现结合肌电图、肌活检可协助诊断儿童型脊肌萎缩症。     

Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy patients

Background:  Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal cord anterior horn cells, leading to muscular atrophy. SMA is clinically classified into three subgroups based on the age of onset and severity. The majority of patients with SMA have homozygous deletions of exons 7 and 8 of the survival motor neuron ( SMN ) gene. The purpose of the present study was to determine the frequency of SMN and neuronal apoptosis inhibitory protein ( NAIP ) gene deletions in Iranian SMA patients. Experience in prenatal diagnosis of SMA in this population is also reported.
Methods:  To study the frequency of deletions of SMN and NAIP genes in an Iranian sample group, 75 unrelated SMA patients (54 type I, eight type II and 13 type III) were analyzed according to the methods described by van der Steege et al and Roy et al .
Results:  Homozygous deletion of SMN1 exons 7 and/or 8 were identified in 68 out of 75 patients (90%). Deletion of exon 5 of the NAIP gene was found in 40/54 of type I, 2/8 of type II and 1/13 of type III patients.
Conclusions:  Deletion of the SMN1 gene is a major cause of SMA in Iran, and NAIP gene deletions were common in the present patients with type I SMA. Also, the incidence of NAIP deletion is higher in more severe SMA.     

Notch信号通路对婴幼儿血管瘤周细胞分化的调控作用

目的 研究Notch信号通路在婴幼儿血管瘤(IH)中的动态表达,探讨其对血管瘤周细胞(Her-pericyte)分化的影响.方法 选取增殖期与消退前期IH瘤体组织.采用免疫荧光双染检测Jagged1、Notch3及Hes1在增殖期与消退前期IH组织中的表达状况.应用Real-time PCR检测增殖期与消退前期Hem-pericyte中Jagged1、Notch3及Hes1基因表达水平.使用Notch信号通路的特异性抑制剂DAPT作用于Hem-pericyte,观察其对Hem-pericyte分化的影响.结果 消退前期IH血管网较增殖期IH血管网排列更为成熟规则.Jagged1、Notch3及Hes1在增殖期与消退前期血管瘤中均有表达,其中Jagged1主要分布于HemEC,Notch3与Hes1则主要表达于Hem-pericyte.与增殖期Hem-pericyte相比,消退前期Hem-pericyte中Notch3与Hes1基因表达水平显著升高(3.10±0.32 vs 1.41±0.37,1.89±0.35 vs 0.78±0.41);与周细胞分化/收缩力相关的基因:smMHC与αSMA的表达水平在消退前期Hem-pericyte中也显著升高(4.27±0.28 vs 0.48±0.19,1.43±0.21 vs 0.39±0.20).采用y-分泌酶抑制剂DAPT阻断Notch信号通路后,消退前期Hem-pericyte中smMHC与αSMA基因的表达水平显著下调(4.31±0.34 vs 2.1±0.32,1.40±0.31vs 0.56±0.27).结论 Hem-pericyte中存在活化的Notch信号通路;Notch参与了对体外培养Hem-pericyte分化的调控.     

INFANTILE MYOFIBROMATOSIS WITH HEMANGIOPERICYTOMA-LIKE FEATURES OF THE TONGUE: A Case Study Including Ultrastructure

We report a case of an infantile myofibromatosis with hemangiopericytoma-like features arising in the tongue of a 5-month-old female infant. Many authors now classify neoplasms as infantile myofibromatosis that were previously called infantile hemangiopericytoma. The ultrastructural features of our tumor illustrate its biphasic nature and provide a possible explanation for its histogenesis. Infantile myofibromatosis, including those diagnosed as infantile hemangiopericytomas, rarely arise in any intraoral location. Despite the generally good prognosis associated with these neoplasms, complete surgical excision is recommended to avoid recurrences.     

脊髓性肌萎缩症患儿骨髓间质干细胞分化为神经元样细胞的实验研究

目的：脊髓性肌萎缩症(SMA)是一组常染色体隐性遗传性疾病,由于SMN基因的缺失或突变,导致脊髓前角细胞变性坏死,引起肢体近端肌肉无力和肌萎缩。该病至今无有效治疗,干细胞治疗可望给患者带来福音。该研究拟探讨SMA患者骨髓间质干细胞（MSCs）能否分化为神经元样细胞,从而为SMA的干细胞治疗提供实验依据。方法：用PCR-RFLP的方法对SMA患者进行基因诊断;分离和纯化患者的（MSCs）,在bFGF预诱导后,再用黄芩甙诱导MSCs分化为神经元样细胞;用神经元标志物NSE和NF鉴定诱导的神经元样细胞。上述研究均与对照者进行对比。结果：PCR-RFLP证实所选患者SMN1基因外显子7缺失,而对照者无缺失;SMA患者和对照者的MSCs形态相同,增殖速度相似;两组MSCs经黄芩甙诱导6 d后,大多数细胞转变为类似于神经元的形态,有长的突起,相互之间连接呈网状。免疫荧光染色鉴定两组分化后的神经元样细胞,NSE和NF均为阳性。结论：SMN1基因缺失不影响MSCs的增殖和分化,SMA患者的MSCs能够分化为神经元样细胞。［中国当代儿科杂志,2007,9（5）：453-456］     

117例儿童脊髓性肌萎缩症自然病史分析

目的 对重庆及周边地区脊髓性肌萎缩症（spinal muscular atrophy,SMA）的自然病史进行分析,为开展SMA的综合管理、基因修饰治疗提供临床依据。 方法 回顾性分析117例SMA患儿的临床资料及生存现状。 结果 117例患儿中,1型SMA 62例（53.0%）、2型45例（38.5%）、3型10例（8.5%）,中位起病年龄分别为2、10、15月龄。1型SMA起病、就诊、确诊时间均早于2、3型SMA（P<0.05）,1型SMA就诊时间窗（起病年龄至就诊年龄）短于2、3型SMA（P<0.05）。肺炎为首发症状、抬头无力、哭声无力、进食费力多见于1型SMA（P<0.05）,2型SMA脊柱侧弯和下肢关节挛缩发生率高于1型（P<0.05）。117例（100%）SMA患儿均为SMN1基因纯合缺失,其中以7号外显子纯合缺失最常见（68.4%,80/117）。1型SMA的6年生存率仅为10%±5%,低于2、3型SMA（P<0.05）。起病年龄≤3月龄、肺炎为首发症状、抬头无力为1型SMA死亡的危险因素（P<0.05）。2型SMA运动能力可呈非线性倒退。 结论 各型SMA患儿临床表现、生存率均存在异质性,1型SMA生存率低,2型SMA运动能力可呈非线性倒退,临床上应早期识别及管理SMA。     

脊髓性肌萎缩症治疗研究进展北大核心CSCD

脊髓性肌萎缩症(spinal muscular atrophy,SMA)是一种常染色体隐性遗传的神经肌肉疾病,主要特征为进行性肌无力和肌肉萎缩。该病是导致患儿在婴幼儿期死亡的首要遗传病。SMA治疗的研究领域近年来发展迅速,部分相关治疗药物已经成功获批上市。该文以SMA近年的治疗研究进展作一综述。     

儿童脊髓性肌萎缩症的基因学研究

目的：研究我国儿童型脊髓性肌萎缩症(SMA)患者的运动神经元生存 (SMN)基因及神经细胞凋亡抑制蛋白 (NAIP)基因外显子的缺失情况,以探讨此二种基因与SMA表型之间的关系。方法：应用PCR和PCR -酶切法检测15例Ⅰ～Ⅲ型SMA患者(Ⅰ型4例,Ⅱ型3例,Ⅲ型8例)、20例表型正常的SMA直系亲属及30例正常对照的SMN基因的第7,8号外显子和NAIP基因的第5 ,6号外显子缺失情况。结果：7例Ⅰ型和Ⅱ型SMA患者中6例纯合缺失SMN基因外显子7和8,1例纯合缺失外显子7而保留外显子8;8例Ⅲ型SMA患者仅1例有外显子7和8的缺失,余7例均无SMN基因的缺失;15例Ⅰ～Ⅲ型SMA患者均未检测到NAIP基因外显子5和 /或 6的缺失。结论：Ⅰ型、Ⅱ型SMA可通过SMN基因第7,8号外显子的检测进行确诊,方法简便可靠,Ⅲ型SMA患者SMN基因缺失率低,故通过检测SMN基因 7,8外显子进行基因诊断尚需谨慎,NAIP基因在SMA发病中的作用尚不清楚,有待进一步研究。     

Safety and efficacy of gene therapy with onasemnogene abeparvovec in the treatment of spinal muscular atrophy: A systematic review and meta-analysis

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease which leads to progressive muscle weakness and atrophy. Our systematic review and meta-analysis aims to explore the efficacy and safety of onasemnogene abeparvovec in SMA patients. We searched PubMed, EMBASE, Web of Science and Cochrane through April 2022. Ten reports enrolling 250 SMA patients were included. CHOP INTEND and motor-milestone significant improvements were detected at both short- and long-term follow-up. Common adverse events included pyrexia, vomiting, thrombocytopenia and elevated aminotransferases. Thrombocytopenia (79.3%, 95%CI: 65.8~90.5) and elevated aminotransferases (71.7%, 95%CI: 62.5~80.1) were more common in SMA patients aged older than 8 months. Despite the paucity of randomized control trial data and low quality of evidence to establish the safety and efficacy of onasemnogene abeparvovec in the treatment of SMA, the data suggest that it is a valuable option for patients with this condition.     

我国脊髓性肌萎缩症多学科管理和诊治模式

脊髓性肌萎缩症(SMA)主要累及运动神经元导致肌无力及肌萎缩,在疾病不同阶段可出现多系统(骨骼、呼吸、消化等)合并症。随着SMA的疾病修正治疗药物在国内的应用及研究的开展,SMA多学科管理及诊治模式迎来了新的挑战。该文从疾病修正药物治疗、康复管理、骨骼管理、营养管理、呼吸管理等方面进行了介绍。     

Psychopathology and familial stress - comparison of boys with Fragile X syndrome and spinal muscular atrophy

BACKGROUND: Chronic illness and mental retardation are both associated with an increased rate of behavioural problems in children and with considerable emotional strain in families. The aim of the study was to analyse and compare the specific effects of two exemplary conditions on familial stress and coping. METHODS: Forty-nine boys with Fragile X syndrome (FXS) were compared with 46 boys with Spinal Muscular Atrophy (SMA) and 32 male controls. Intelligence was measured with the RAVEN or K-ABC tests. Psychopathology was assessed with the CBCL questionnaire and a structured psychiatric interview (Kinder-DIPS), parental stress with the QRS, coping with the F-COPES and social support with the F-SOZU questionnaires. RESULTS: The mean age of the FXS boys was 8.6, of the SMA boys 12.7 and of the controls 11.2 years. The mean IQ was 47 for the FXS, 112 for the SMA and 103 for the control groups. According to the CBCL, 89.8% of the FXS boys, 21.7% of the SMA and 15.7% of the controls had a total score in the borderline or clinical range. The rates were 63.3%, 34.8% and 21.9% for internalising and 67.3%, 10.9% and 18.8% for externalising behaviour, respectively. 81.6% of the FXS and 10.9% of the SMA patients had a DSM-IV or ICD-10 psychiatric diagnosis. The most common were ADHD (FXS: 36) and Separation Anxiety Disorder (SMA: 4). In total, parental stress was significantly higher in the FXS than in the SMA families (and in both compared to controls). There were no major inter-group differences regarding social support and familial coping. CONCLUSIONS: Children with FXS are severely mentally retarded and have a high rate of mainly externalising disorders. Despite good coping abilities and social support, this is associated with high familial stress. The SMA boys, with an intelligence in the upper normal range, are no more deviant than their healthy controls. Parental stress is lower in the SMA families with good coping abilities. In conclusion, families with mentally retarded children are in even greater need of help than those of children with severe chronic illness/physical handicap.     

疑似脊髓性肌萎缩症患儿338例的运动神经元存活基因分析

目的 研究儿童脊髓性肌萎缩症(SMA)运动神经元存活基因SMN1缺失和诊断的意义.方法 根据国际诊断标准、病例随访和基因分析结果对338例疑似SMA的患儿进行诊断和分型.应用PCR-酶切方法分析患儿SMN1基因外显子7和外显子8的纯合缺失.应用等位基因特异PCR结合变性高效液相色谱分析(DHPLC)方法分析患儿的SMN1基因拷贝数,确定杂合缺失.结果 (1)确诊SMA 267例,其中Ⅰ型143例,Ⅱ型82例,Ⅲ型42例,分别占53.6%、30.7%和15.7%.(2)267例SMA患儿的SMN1基因缺失分析显示:SMN1基因外显子7和8均纯合缺失为183例,占68.5%(183/267),仅外显子7纯合缺失,外显子8不缺失为34例,占12.7%(34/267),外显子7杂合缺失为33例,占12.4%(33/267),非缺失为17例,占6.4%(17/267),未见SMN1基因外显子8的单独缺失.(3)Ⅰ型和Ⅱ型SMN1基因缺失率相近.Ⅲ型SMN1基因纯合缺失率较低于Ⅰ型和Ⅱ型,杂合缺失率较高于Ⅰ型和Ⅱ型.结论 (1)我国儿童SMA的SMN1基因纯合缺失和杂合缺失频率提示,SMN1基因突变存在种族异质性,SMN1基因内微小突变需要研究.(2)SMN1基因诊断具有特异性和无创性,80%SMA患儿通过SMN1基因纯合缺失分析得到诊断.(3)Ⅲ型SMA的临床诊断和基因分析需要进一步研究.     

儿童脊髓性肌萎缩症的基因诊断

目的探讨儿童脊髓性肌萎缩症(SMA)的特异性基因诊断方法。方法应用聚合酶链反应-限制性片段长度多态性(PCR—RFLP)技术.对19例临床诊断为SMA患儿及21名健康儿童的运动神经元存活(SMN)基因进行检测。结果SMA患儿SMN基因的第7和第8号外显子均缺失,健康儿童SMN基因的第7和第8号外显子均未缺失。结论检测SMN基因第7和第8号外显子缺失的方法可用于SMA的基因诊断,且PCR—RFLP技术对SMA的诊断具有较高的特异性和敏感性。     

Gait in children with infantile/atypical autism: Age-dependent decrease in gait variability and associations with motor skills

Gait and its associations with prewalking motor milestones, motor skills, and age were investigated in 32 children with infantile/atypical autism and 36 typically developing controls. Gait was assessed using GAITRite recordings of spatiotemporal and variability gait parameters. Parents reported their child's prewalking motor milestones. Motor skills were assessed using the Movement Assessment Battery for Children. Children with infantile/atypical autism showed higher gait variability than controls, indicating a less regular walking pattern. In children with infantile/atypical autism gait variability was negatively associated with motor skills, but there was no such association with prewalking motor milestones. The higher gait variability in children with infantile/atypical autism showed an age-dependent decrease, suggesting that their gait regularity converges toward that of typically developing children.     

儿童脊髓性肌萎缩合并肺部感染36例诊治分析

目的　总结儿童脊髓性肌萎缩合并肺部感染的临床特征,提高临床医生对该病的认识,改善预后。方法　回顾性分析温州医科大学附属第二医院育英儿童医院2008年1月1日至2017年12月31日收治的36例脊髓性肌萎缩症（SMA）合并肺部感染患儿的临床资料。结果　36例中Ⅰ型19例,Ⅱ型9例,Ⅲ型 8例。临床表现和体征以发热、咳嗽、气促或呼吸费力、三凹征、肺部细湿啰音等多见。有11例患儿出现呼吸衰竭,其中Ⅰ型SMA患儿7例（63.6%）,Ⅱ型SMA患儿2例（18.2%）,Ⅲ型SMA患儿2例（18.2%）。5例SMA患儿影像学检查提示脊柱侧弯,3例为Ⅱ型SMA患儿,2例为Ⅲ型患儿。有18例患儿病原学检测阳性,Ⅰ型SMA患儿10例（55.5%）,Ⅱ型SMA患儿4例（22.2%）,Ⅲ型SMA患儿4例（22.2%）,以院内条件致病菌混合感染多见,其中洋葱伯克霍尔德氏菌最常见。3例患儿在院内死亡,22例患儿好转出院,其余11例患儿放弃治疗。住院治疗的次数,重症肺炎、呼吸衰竭的发生率在前、后5年的比较差异均有统计学意义（P＜0.05）。结论　SMA极易并发肺部感染,要警惕条件致病菌感染,对呼吸衰竭者及时使用机械通气。积极有效的呼吸道护理,对减少肺部感染发生,改善SMA患儿的预后有积极的影响。     

Spinal muscular atrophy: an update

Spinal muscular atrophy (SMA) is the most common childhood neurodegenerative disease. We report an infant with SMA type 1 and discuss the recent developments in SMA genetics, pathophysiology, and possible treatment options. Because SMA type 1 remains a fatal illness for which there is not yet a cure, the focus of patient care continues to be symptomatic. Thus, the most appropriate aspects of care at present and future are also discussed.     

新生儿、小婴儿化脓性脑膜炎73例

目的探讨新生儿、小婴儿化脓性脑膜炎（化脑）的临床表现、转归及早期识别方法。方法对73例确诊为化脑的3个月龄以下婴儿进行回顾性分析。按照发病年龄分为新生儿、小婴儿组,对二组临床症状、惊厥发作类型、并感染情况、病原学检测结果、头颅影像学检查情况、并发症、感染项目检测结果及临床转归进行比较。结果新生儿、小婴儿化脑均以体温改变、精神反应异常、纳差、惊厥为主要表现,惊厥发作类型中新生儿组微小发作较婴儿组显著增多（P〈0.01）,婴儿组强直和阵挛型发作较新生儿显著增多（Pa〈0.01）;新生儿组并败血症者较婴儿组显著增多（P〈0.01）;小婴儿化脑并发症发生率较新生儿显著增高（P〈0.01）;婴儿组发生硬膜下积液者较新生儿组显著增多（P〈0.01）。二组预后不良患儿就诊时间较痊愈患儿就诊时间晚,有显著性差异（Pa〈0.01）。结论新生儿、小婴儿化脑危害严重,化脑的早期识别依赖于临床观察,及时脑脊液检查。婴儿易发生硬膜下积液。     

脊髓性肌萎缩症患儿SMN1和SMN2基因拷贝数与临床表型的相关性分析

目的 对脊髓性肌萎缩症（SMA）患儿的运动神经元存活基因1（SMN1）和SMN2拷贝数与临床表型之间的关系进行分析,提高对SMA患儿的早期诊断和临床干预水平。方法 选取45例SMA患儿,应用多重连接依赖性探针扩增技术对SMN1和SMN2基因拷贝数进行检测,分析SMN基因拷贝数同临床表型之间的关系。结果 45例SMA患儿中,SMN1第7和8外显子纯合缺失者为42例,占93%（42/45）;仅有第7外显子缺失者为3例,占7%（3/45）。SMA不同临床分型和SMN1基因第7、8外显子缺失类型间无相关性（P > 0.05）;SMA患儿和健康儿童的SMN2基因拷贝数分布差异有统计学意义（P < 0.05）,前者以2和3拷贝者居多,后者以1和2拷贝者居多;不同SMA临床分型间SMN2拷贝数分布差异有统计学意义（P < 0.05）,SMN2基因为2拷贝者发病年龄明显小于3和4拷贝者。Ⅰ型SMA患儿中SMN2拷贝数以2或3拷贝者居多,Ⅱ型以3拷贝者居多,Ⅲ型以3或4拷贝者居多。随着SMN2拷贝数增加,患儿发病年龄越大,保有的运动功能和临床结局越好,SMN2基因拷贝数同临床结局间的关系存在显著性差异（P < 0.05）。结论 SMN2基因通过剂量补偿效应减轻SMA疾病严重程度,SMN2拷贝数同SMA临床表型具有相关性,可将其作为预测疾病严重程度的依据之一。     

Physician attitudes towards ventilatory support for spinal muscular atrophy type 1 in Australasia

BACKGROUND: Without ventilatory support, premature death from respiratory insufficiency is virtually universal in infants with spinal muscular atrophy type 1 (SMA1). With mechanical ventilation, however, long-term survival has been reported from numerous international centres. We aimed to characterize physician attitudes to the various forms of ventilatory support for children with SMA1. METHODS: We surveyed neurologists, respiratory physicians, clinical geneticists and intensivists from all major paediatric hospitals in Australia and New Zealand regarding their views on ventilatory management of SMA1. RESULTS: Ninety-two of the 157 (59%) physicians surveyed replied. Respondents included 16 clinical geneticists, 19 intensive care physicians, 28 neurologists and 29 respiratory physicians. Almost half (47%) opposed invasive ventilation of children with SMA1 and respiratory failure precipitated by intercurrent illness. The majority (76%) opposed invasive ventilatory support for chronic respiratory failure in SMA1. In contrast, non-invasive ventilation was felt by 85% to be appropriate for acute respiratory deteriorations, with 49% supporting long-term non-invasive ventilatory support. Most physicians felt that decisions regarding ventilation should be made jointly by parents and doctors, and that hospital Clinical Ethics Committees should be involved in the event of discordant opinion regarding further management. A majority felt that a defined hospital policy would be valuable in guiding management of SMA1. CONCLUSIONS: Respiratory support in SMA1 is an important issue with significant ethical, financial and resource management implications. Most physicians in Australian and New Zealand oppose invasive ventilatory support for chronic respiratory failure in SMA1. Non-invasive ventilation is an accepted intervention for acute respiratory decompensation and may have a role in the long-term management of SMA1. Clinical Ethics Committees and institutional policies have a place in guiding physicians and parents in the management of children with SMA1.