杜氏肌营养不良与骨骼肌纤维化

骨骼肌纤维化是杜氏肌营养不良杜氏肌营养不良的主要病理变化之一,可影响肌纤维的再生、收缩功能,加重病情,在骨骼肌纤维化的发生发展过程中,炎症细胞、成纤维细胞、成肌纤维细胞及其分泌的细胞因子起重要作用.该文对杜氏肌营养不良的骨骼肌纤维化研究进展进行综述.     

应用血肌酸激酶或肌酸激酶MM同工酶筛查新生儿杜氏肌营养不良症的系统评价/Meta分析

背景：目前应用血CK或其同工酶（CK MM）筛查新生儿杜氏肌营养不良症（DMD）的临床研究较少,其准确性尚不明确。 目的：系统评价血CK或CK MM筛查新生儿DMD的准确性。 设计：系统评价/Meta分析。 方法：检索Medline（PubMed）、Embase、Cochrane Library、Web of Science、Scopus、中国知网数据库、中国生物医学文献数据库、万方数据库和维普中文期刊全文数据库,检索起始时间均为1975年1月1日,Medline（PubMed）检索截止时间为2022年11 月5日,其他数据库检索截止时间为2022年10月5日。纳入以血CK或CK MM筛查新生儿DMD的诊断准确性研究。采用QUADAS 2量表对纳入文献进行偏倚风险及临床适用性评价;提取文献数据,应用Stata 15.0和Meta Disc 1.4软件进行Meta分析;合并敏感度、特异度、阳性似然比（PLR）、阴性似然比(NLR)、诊断比值比(DOR),并绘制综合受试者工作特征曲线（SROC）,计算AUC和Q指数值。 主要结局指标：敏感度和特异度。 结果：CK筛查DMD纳入11篇文献,共1 351 953例新生儿;敏感度97%（95%CI:88%～99%）,特异度100%（95%CI:100%～100%）,PLR 1 131（95%CI:370～3 455）,NLR 0.01（95%CI:0.00～0.19）,DOR 16 476 (95%CI:4 115~65 963),AUC为0.995 4,Q指数为0.974 0;Deeks检验P=0.12,发表偏倚的可能较小。CK MM筛查DMD纳入5篇文献,共156 547例新生儿;敏感度和特异度均为100%（95%CI:100%~100%）,PLR 3 925（95%CI: 3 925~3 925）,NLR 0.00（95%CI:0.00~0.00）,DOR 23 094 (95%CI:5 773~92 384);AUC为0.925 2,Q指数为0.859 4。 结论:应用血CK或CK MM筛查新生儿DMD的准确性高,有助于早期诊断DMD。     

杜氏肌营养不良患者心脏损害的研究进展

杜氏肌营养不良是儿童致死性肌萎缩性疾病。该疾病发病率低、进展迅速、医生认识有限以及呼吸衰竭的有效治疗等多种因素,使心力衰竭成为杜氏肌营养不良患者死亡的首要原因。早期发现、诊治杜氏肌营养不良患者的心脏损害,对于延长患者生存时间和改善生活质量具有重要意义。该文就近年来杜氏肌营养不良患者心脏损害的流行病学、发病机制、早期诊断技术、预防和治疗等方面的研究进展作一综述。     

杜氏肌营养不良患儿的相关基因研究

目的　对确诊为杜氏肌营养不良 (DMD)患儿血清进行基因和肌酸磷酸激酶 (CPK)检测 ,以研究DMD的基因缺失情况以及与CPK的关系。方法　①采用多重引物PCR的方法检测基因缺失 ;②应用多功能全自动生化仪检测CPK。结果　① 30例患儿中基因缺失者 17例 (5 6 7% ) ,单一缺失者 8例 (47 1% ) ,多重缺失 9例(5 2 9% )。其中外显子 5 1缺失占 6 4 7% (11人次 ) ,其次为 4 8缺失占 5 2 9% (9人次 ) ;4 5缺失占 35 2 % (6人次 ) ;4 4缺失占 17 6 % (3人次 ) ;12缺失占 11 8% (2人次 ) ;外显子 8、17、19缺失各 1人次 ,各占 5 9%。②外显子缺失者CPK(1196 2 78± 6 30 5 6 5 )IU/L与无外显子缺失者CPK (95 37 6 9± 4 30 3 85 )IU/L相比 ,单一缺失者CPK(1170 4 6 5± 6 5 6 1 10 )IU/L与多重缺失者CPK(12 192 2 2± 6 0 96 80 )IU/L比较 ;单纯外显子 5 1缺失CPK(135 4 2 10± 5 5 73 93)IU/L与外显子 5 1缺失合并 4 8缺失者CPK(12 2 16 2 5± 6 833 75 )IU/L相比 ,三组均P >0 0 5 ,无显著性差异。结论　①应用PCR技术检测DMD基因缺失检出率较高 ,多重缺失占 4 7 1% ,其中以外显子 5 1、4 8、4 5缺失最多见 ;②外显子缺失与否或缺多少与CPK增高程度无相关性     

6例杜氏肌营养不良回顾性分析

目的分析6例杜氏肌营养不良(DMD)患儿的临床特点,并结合文献复习,为早期诊断该病及采取有效治疗措施进行归纳总结。方法收集2010年1月至2015年10月收治的6例DMD患儿的临床资料,进行回顾性分析。结果 6例均为男性,确诊年龄1.2~11.5岁,均无家族史。起病隐匿,均有谷丙转氨酶、谷草转氨酶、乳酸脱氢酶、α-羟丁酸脱氢酶、肌酸激酶、肌酸激酶同工酶同步升高,以肌酸激酶升高最显著、为正常的3.7~107.2倍。基因检测均提示DMD基因突变;其中2例患儿的母亲行基因检测,提示携带相同突变基因。1例行肌肉活检,病理结果符合DMD改变。1例患儿行脐血间充质干细胞移植,5 d后肌酸激酶下降77.0%。结论对血清肌酶异常、运动功能异常的男童,应高度警惕DMD,尽早行CK及基因检测确诊,尽早干预,保护尚存的正常肌纤维,延缓疾病进展。     

反义寡核苷酸在杜氏肌营养不良基因治疗中的应用

杜氏肌营养不良（DMD）是一种致死性X染色体连锁隐性遗传病，发病率高，患者多在30岁左右因心力衰竭和呼吸衰竭而死亡。近年来，在众多对DMD基因治疗方案中，反义寡核苷酸凭借其在肿瘤治疗和病毒控制中显示出的良好应用前景而受到研究人员的关注，他们利用反义寡核苷酸诱导基因中的特异外显子缺失以调控突变基因的表达，以此达到恢复具有功能的抗肌萎缩蛋白表达，并使DMD得到控制和治愈的目的。     

杜氏肌营养不良转化医学和康复护理上海国际研讨会通知

由复旦大学附属儿科医院主办的国家级继续医学教育项目＂杜氏肌营养不良转化医学和康复护理上海国际研讨会＂,将于2013年10月20～21日举办。本次研讨会邀请美国卡罗莱纳医疗中心、日本国立精神神经医疗研究中心医院杜氏肌营养不良诊疗团队授课,会议主题涉及杜氏型肌营养不良患儿的激素治疗,呼吸和心功能的监测,康复护理,营养,     

肌特异性microRNA作为杜氏肌营养不良生物标志物的研究进展

microRNA（miRNA）是一种长度约22nt的非编码单链RNA,主要在转录后调控基因的表达。目前miRNA已成为多种疾病潜在的生物标志物,如肿瘤、白血病、神经系统疾病等。肌特异性miRNA在杜氏肌营养不良（DMD）患者的骨骼肌中富集,且在DMD发病机制中起重要作用。鉴于肌酸激酶诊断DMD的特异性有限,如其水平与病情轻重无明显关联,故探索肌特异性miRNA是否能成为理想的DMD生物标志物具有重要临床意义,该文将对这一领域研究进展进行综述。     

杜氏肌营养不良转化医学和康复护理上海国际研讨会通知

由复旦大学附属儿科医院主办的国家级继续医学教育项目“杜氏肌营养不良转化医学和康复护理上海国际研讨会”,将于2013年10月20-21日举办。本次研讨会邀请美国卡罗莱纳医疗中心、日本国立精神神经医疗研究中心医院杜氏肌营养不良诊疗团队授课,会议主题涉及杜氏型肌营养不良患儿的激素治疗,呼吸和心功能的监测,康复护理,营养,遗传咨询,外显子跳跃治疗,国际患者注册登记等。授予I类学分10分。会议地点：复旦大学附属儿科医院（上海市闵行区万源路399号）5号楼报告厅。本次研讨会收取注册费800元,包括午餐和资料费。住宿统一安排,费用自理。     

Duchenne muscular dystrophy: Recent concepts

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease, affecting only males and transmitted by females. Recent proposed pathogeneses are defective DNA repair mechanism and cell-mediated cytotoxicity. Serum CPK estimation is most frequently high (30–300) and is also reliable for detecting carriers. It is important to recognise the affected boys as early as possible. Diagnosis of DMD is made from clinical features, CPK estimation, EMG and ECG abnormalities. The use of agents to reduce influx of intracellular calcium in patients with DMD are emerging for therapeutic consideration. New advance in genetic counselling is the localisation of the gene for DMD using DNA polymorphisms.     

Cardiomyopathy of Duchenne muscular dystrophy

Summary A total of 18 male patients with Duchenne muscular dystrophy (DMD), aged 8–29 years (mean, 15.7 years), were prospectively studied to assess the cardiomyopathy associated with DMD, using clinical parameters and noninvasive cardiovascular investigations: electrocardiogram (ECG), Holter monitoring, and echocardiography. In addition, five clinical tests of cardiovascular autonomic function were used to assess the role of the autonomic nervous system in the pathogenesis of dysrhythmias.The majority of subjects were asymptomatic, but four had abnormal physical findings. All had abnormal ECG, the commonest abnormality (in 16) being tall R waves or increased R/S ratios in the right precordial leads; 14 had abnormal findings on echocardiography, including three with poor left ventricular function and five with mitral valve prolapse (MVP). Labile abrupt sinus tachycardia was present in 11, and four had high-grade ventricular ectopy. None had definite clinical evidence of autonomic dysfunction.The cardiomyopathy of DMD appears to be unrelated to disease severity. However, abnormal Q waves or Q/R ratios in ECG leads I, a V_L, and V₅–V₆ are significantly related to young age (p<0.05), and high-grade ventricular ectopy occurred significantly more frequently (p<0.05) in older subjects (>15 years). Dysrhythmias were not related to the presence of MVP, poor left ventricular function, or autonomic dysfunction.     

Spontaneous deep venous thrombosis in Duchenne muscular dystrophy

Deep venous thrombosis (DVT) is an uncommonly encountered condition in childhood and, as a consequence, the diagnosis may be overlooked. We describe the first two cases of DVT occurring in children with Duchenne muscular dystrophy. Both brothers were wheel-chair-bound for protracted periods. The first case occurred following spinal fusion for scoliosis. The second occurred spontaneously following immobilisation in hospital while undergoing investigation for a ureteric stone. Serological investigations to outrule an underlying thrombogenic cause showed no deficiency of protein C or antithrombin III nor the presence of lupus anticoagulant in either patient. The presence of flaccid lower extremities resulting in prolonged immobilisation combined with an ineffective muscle pump for venous return may have predisposed the patients in our series. The issue of prophylaxis should now be actively considered in such patients in high-risk circumstances. Correspondence to: R. Fitzgerald     

Communication regarding breathing support options for youth with Duchenne muscular dystrophy

BACKGROUND:

Ventilators for home use, manual and mechanically assisted coughing techniques, and the services of in-home respiratory therapists are options for youth with Duchenne muscular dystrophy (DMD). Evidence supports the use of these modalities, but there seems to be few youth who are receiving these therapies. Is there a knowledge transfer issue? Is there a lack of resources? What is the best way to discuss the issues? What do youth and parents want?

OBJECTIVE:

To determine practices, attitudes and beliefs regarding the timing and content of client/family communication related to ventilatory support decisions for individuals with DMD.

METHODS:

A questionnaire was sent to all 19 children’s treatment centres in Ontario. The lead clinician responded on behalf of his or her centre. Another questionnaire was given to 11 families who attended a parent support meeting.

RESULTS:

Respondents from the treatment centres who provide services for youth with DMD indicated that there are resources in terms of personnel and an obligation to provide information about ventilatory support, but provision of information is often late and/or inconsistent. The family respondents wanted more information and they wanted it earlier than they are currently receiving it.

CONCLUSIONS:

Parents and youth dealing with DMD have many resources at their disposal in Ontario. The evidence is clear that there are long-term health benefits to providing ventilatory support as well as instruction in coughing assistance. Due to the classical nature of disease progression in DMD, information should be provided within reasonable timelines.     

Duchenne muscular dystrophy

Duchenne muscular dystrophy, an X‐linked disorder, has an incidence of one in 5000 boys and presents in early childhood with proximal muscle weakness. Untreated boys become wheelchair bound by the age of 12 years and die of cardiorespiratory complications in their late teens to early 20s. The use of corticosteroids, non‐invasive respiratory support, and active surveillance and management of associated complications have improved ambulation, function, quality of life and life expectancy. The clinical features, investigations and management of Duchenne muscular dystrophy are reviewed, as well as the latest in some of the novel therapies.     

Short stature: a common feature in Duchenne muscular dystrophy

In a retrospective growth evaluation, which included parental height, birth length and a longitudinal analysis of growth and bone maturation, it has been shown that short stature is a common finding in Duchenne muscular dystrophy already in an early or even preclinical stage. Normal length and weight at birth, slow subsequent growth with a curve crossing the centiles in the 1st years of life, and normal bone maturation are characteristic of this type of short stature.Abbreviations DMD Duchenne muscular dystrophy - SD standard deviation - SDS standard deviation scores - SEM standard error of the mean - MP mean mid-parent height - M mean height of fathers (male) - F mean height of mothers (female) - Xp short arm of the X-chromosome Presented in part at the annual meeting of the Swiss Paediatric Society 1985 in Zürich