晚发型糖原贮积病Ⅱ型1例患者的临床和病理及其家系GAA基因分析

目的研究1例晚发型糖原贮积病Ⅱ型(GSDⅡ)患者的临床、病理和遗传特征。方法回顾性分析1例晚发型GSDⅡ患者的临床资料和骨骼肌病理特征,同时取得患者和家属知情同意后对其家系进行遗传咨询,提取外周血白细胞基因组DNA,应用聚合酶链反应(PCR)扩增酸性-α-葡萄糖苷酶(GAA)的基因编码区,直接测序分析GAA基因突变情况。结果 1患者男性21岁,临床表现为呼吸肌、四肢近端肌无力。肌电图提示肌源性损害。三角肌病理和免疫组化染色提示肌源性损害,酸性磷酸酶染色(+)。血GAA活性明显低于正常,符合晚发型GSDⅡ诊断。2家系GAA基因分析提示,患者及其父亲和2位姑姑(父亲的妹妹)均携带一个未见报道的GAA基因新突变:位于第8号外显子的缺失突变(p.Met439del);患者及其母亲、外祖母均携带一个已报道的GAA基因16号外显子错义突变(p.Trp746Cys);该家系中发现一些非致病性杂合突变。结论在晚发型GSDⅡ家系中发现一个新的GAA基因第8号外显子缺失突变p.Met439del。先证者因存在双杂合突变导致GAA活性下降并出现晚发型GSDⅡ的临床和病理改变。     

糖原累积病Ⅱ型的诊治进展

糖原累积病Ⅱ型(又称Pompe病)是一种常染色体隐性遗传的先天代谢性疾病,为编码酸性α-糖苷酶(GAA)的基因发生突变,导致溶酶体内糖原分解障碍并广泛沉积于全身所致.该病临床表现复杂多样,包括婴儿型和晚发型两大类,发病率约1/40 000[1].1994-2011年国内共报道50余例Pompe病.本文主要对Pompe病的临床表现、发病机制及诊治进展方面做一回顾性介绍.     

Friedreich共济失调的临床特征及GGA三核苷酸重复突变分析

目的研究弗里赖希共济失调(FRDA)的临床特征和X25基因(GAA)n重复序列突变.方法应用聚合酶链反应(PCR)技术结合琼脂糖凝胶电泳分析,对2个临床诊断为(FRDA)的2例患者及4例家系成员进行X25基因(GAA)n重复序列和FRDA患者的临床特征进行分析.结果2例患者及4例家系成员均证实PCR产物大小为500 bp,均为纯合子,其等位基因片断中(GAA)n重复序列拷贝数为13个,排除了X25基因(GAA)n突变.2例患者主要表现为进行性躯干共济失调,并首次报道伴随癫痢发作.结论FRDA具有一定的临床和遗传异质性,遗传学分析可以明确诊断.     

晚发型Pompe病患者的临床、病理及GAA基因突变特点

目的探讨1例晚发型Pompe病(LOPD)患者的临床、病理特点及酸性α-葡萄糖苷酶(GAA)基因突变特点。方法分析1例LOPD患者的临床资料,对患者进行右股四头肌活检,并应用PCR产物直接测序法进行GAA基因所有外显子及其侧翼序列的突变检测,采用逆转录PCR法观察突变位点对mRNA剪切的影响。结果患者23岁女性,主要表现为II型呼吸衰竭及体重指数显著降低,伴肺动脉高压、右心功能不全及四肢近端无力。骨骼肌病理检查发现肌纤维内出现大量嗜碱性空泡,部分空泡内可见糖原物质沉积。GAA基因分析显示患者存在错义突变c.2238G>C及剪切突变c.1551+3_c.1551+6del AAGT,后者导致mRNA上第10号外显子缺失。结论发现1例LOPD患者中存在新突变c.1551+3_c.1551+6del AAGT,该患者主要表现为严重的呼吸功能障碍伴低体重。     

细丝蛋白C肌病基因存在新的插入缺失突变

目的 报道在1个细丝蛋白C(filamin C,FLNC)肌病家系中发现的新的插入缺失突变.方法 该家系连续5代共有19例患者,临床和病理资料在前期研究中已经作为肌原纤维肌病进行了报道.现对包括先证者在内的3例患者、5名无症状家系成员和50名健康人进行FLNC基因的测序,利用质粒将FLNC基因的第18号外显子扩增产物进行克隆分离,然后进行电泳鉴定和直接测序.结果 先证者的FLNC基因的第18号外显子存在18个正常碱基缺失,同时插入6个异常碱基,导致FLNC蛋白第7个免疫球蛋白样杆状重叠结构异常,继而致FLNC蛋白结构的失稳.家系中另2例患者存在同样的突变,而5名无症状家系成员和50名健康对照均正常.结论 FLNC肌病存在FLNC基因第18号外显子新的插入缺失突变,我们发现该病可以出现在德国之外的其他种族.     

X连锁Charcot-Marie-Tooth病1型六个家系的病理和基因突变特点

目的 报道6个X连锁Charcot-Marie-Tooth病1型(CMTX1)家系的神经病理和基因型改变特点.方法 6个CMTX1家系的先证者均为男性,发病年龄11 ～24岁,出现下肢远端为主的肌无力、腱反射减低和轻度感觉减退.先证者1伴随发作性白质脑病,先证者5伴随小脑性共济失调.12名家系成员也出现周围神经损害症状,另7名存在高弓足或腱反射减低.对6例先证者行腓肠神经活体组织检查,并对6例先证者、8名受累家庭成员和10名无症状家系成员及50名健康女性进行缝隙连接蛋白32( Cx32)基因测序.结果 6例先证者有髓神经纤维出现轻-中度减少伴轴索再生变性,5例出现薄髓鞘神经纤维,其中3例伴洋葱球样结构,2例伴炎细胞浸润.6个家系的Cx32基因存在5种新突变和1种同义突变,即L20T、I127F、D178G、A197V错义突变,403_404T insT插入突变和L10L沉默突变,10名无症状家系成员中有4名女性为携带者,6名男性和健康对照均没有这些基因突变.结论 该组CMTX1患者的周围神经病理改变以慢性轴索损害为主,Cx32基因较多新突变的出现提示我国CMTX1患者具有个体突变特点.     

结蛋白基因S12F新突变导致的结蛋白病一家系

目的 报道1个结蛋白基因新突变导致的结蛋白病家系,介绍其临床和病理改变特点.方法 1个常染色体显性遗传家系内共有8例患者,男7例,女1例.发病年龄20～50岁.其中7例有心脏损害,3例有肢体近端无力,1例伴慢性腹泻.先证者和其兄行左肱二头肌活体组织检查,进行组织学、酶组织化学、电镜观察及抗结蛋白等免疫组织化学染色.先证者和3例患者、5名无症状家系成员及50名健康人行结蛋白基因测序.结果 先证者的骨骼肌出现肌纤维直径变异加大伴结缔组织增生,少数肌纤维出现嗜酸性改变伴镶边空泡,其兄的骨骼肌仅在许多肌纤维内出现小圆状嗜酸性包涵体.肌纤维内包涵体和肌纤维膜下结蛋白阳性.电镜显示先证者肌纤维内颗粒物质沉积.4例患者存在结蛋白基因S12F突变,无症状家系成员和健康对照无此突变.结论 结蛋白S12F新突变导致的结蛋白病多出现在男性,以心脏病多见.病理改变在家系不同患者之间存在差异.     

脑池及脑室出血为主的颅脑损伤27例临床分析

目的分析有明确外伤病史,CT表现为脑池及脑室出血为主的颅脑损伤患者的影像资料,提高颅脑损伤合并脑血管病的诊断,减少漏诊。方法回顾分析我院神经外科自2012-06—2014-06间颅脑CT表现为脑池及脑室出血为主的27例颅脑损伤患者的影像资料,对其CTA或DSA诊断的结果进行分析。结果 27例患者男19例,女8例,年龄23~74岁,平均(49±9.8)岁。25例均行CTA或DSA检查,发现无阳性14例,阳性11例(颅内动脉瘤5例,多发颅内外血管严重狭窄或闭塞3例,脑动静脉畸形2例,烟雾病1例)。结论以脑池及脑室出血为主的颅脑损伤病人应常规进行CTA或DSA的检查,减少对脑血管病的漏诊。     

伴PSEN2基因V214L突变的早发型阿尔茨海默病一家系临床研究

目的 报道1例伴PSEN2基因V214L突变的早发型阿尔茨海默病患者的临床表型和基因变异特点,并进行家系分析。方法与结果 男性先证者,58岁发病,病程5年,以记忆力减退为首发表现,症状进行性加重,无痴呆家族史。简易智能状态检查量表评分1分,蒙特利尔认知评价量表评分为零,日常生活活动能力量表评分71分,Hachinski缺血评分3分。头部MRI显示大脑皮质广泛萎缩,以双侧海马萎缩显著,深部脑白质多发高信号（Fazekas分级2级）。痴呆相关基因外显子高通量测序显示,先证者及其妹均存在PSEN2基因第8号外显子c.640G> T(p.V214L)杂合错义突变和SORL1基因第28号外显子c.3815-4A> C杂合剪接突变。先证者最终诊断为伴PSEN2基因V214L突变的早发型阿尔茨海默病,其妹考虑为阿尔茨海默病绝对风险人群,该家系明确为早发型阿尔茨海默病家系。结论 PSEN2基因V214L突变很可能导致早发型阿尔茨海默病,尚待研究证实该突变对β-淀粉样蛋白40和42的影响以验证其致病性。     

GNE基因新发突变致GNE肌病一例临床表型及生物信息学分析

目的报告1例GNE肌病患者,总结其临床表型和基因型特征,扩展GNE基因突变谱。方法与结果男性患者,33岁,双下肢远端对称性无力,以小腿前群肌显著,缓慢进展;父母为近亲婚配;血清肌酸激酶升高(1139U/L);肌电图呈肌源性损害;双下肢CT显示轻度肌萎缩;肌肉组织活检可见肌纤维大小不等,肌细胞核内移,约2%的肌纤维存在镶边空泡;基因检测显示,患者存在GNE基因外显子9 c.1624CT(p.Pro542Ser)纯合突变,其母、其子和其女均携带GNE基因外显子9 c.1624CT(p.Pro542Ser)杂合突变,该突变尚未报道,经生物信息学分析判断为有害,根据美国医学遗传学和基因组学会指南判断为Ⅱ类可能的致病性突变。患者最终明确诊断为GNE肌病,该家系明确诊断为GNE肌病家系。结论本研究系统报道1例GNE肌病患者的基因型和临床表型信息,扩展GNE基因突变谱,加深临床医师对疾病的认识。     

Mortality of patients with parkinson's disease treated with levodopa

Summary The effect of levodopa on the mortality of patients with Parkinson's disease was investigated in 349 patients treated with levodopa or levodopa combined with a decarboxylase inhibitor during 1969–1975 inclusive. During the study period, 61 patients died. The expected mortality was 32.99 resulting in a ratio of actual to expected deaths of 1.85. The excess mortality was accounted for by patients with a severe disease at entry and especially, by the less favorable effect of levodopa treatment than in the living patients. In comparison with the prelevodopa era, the reduction of mortality and the increase of life expectancy of patients with Parkinson's disease during levodopa treatment possibly reflect the decrease of the early mortality due to Parkinson's disease.

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Zusammenfassung Die Auswirkung der Levodopa-Behandlung auf die Mortalität von Parkinson-Patienten wurde anhand einer Serie von 349 Fällen untersucht, welche in den Jahren 1969–1975 einerseits mit L-Dopa, andererseits mit L-Dopa zusammen mit Decarboxylasehemmern behandelt wurden. Während der Beobachtungsperiode verstarben 61 Patienten. Die erwartete Mortalität hätte 32,99 betragen müssen, was eine Relation von tatsächlicher zu erwarteter Mortalität von 1,85 ergibt. Für die höhere Mortalität waren Fälle verantwortlich mit schweren Krankheitserscheinungen bei Beginn der Therapie und im besondern auch mit einem geringeren Effekt der L-Dopa-Therapie als bei den überlebenden Patienten. Verglichen mit den Beobachtungen vor Einführung der L-Dopa-Therapie beruht wohl die Verminderung der Mortalität und die erhöhte Lebenserwartung von Parkinson-Patienten unter L-Dopa auf der Abnahme der Frühtodesfälle durch die Parkinson'sche Krankheit.

     

Creutzfeldt-Jakob disease with plaques and paired helical filaments

A 32-year-old man with rapidly progressive dementia, pyramidal signs, myoclonic jerks and dystonic movements died following brain biopsy. neuropathological examination revealed minimal neuronal loss accompanied by mild spongiform change and astrocytic reaction. Numerous plaques and neurofibrillary tangles composed of paired helical filaments dominated the ultrastructural picture. This patient had features of both Creutzfeldt-Jakob disease and Alzheimer's disease, providing additional support for the existence of an overlap between these disorders.     

Relationship of illness perceptions with depression among individuals diagnosed with lupus

Background: The purpose of this study was to investigate the relationship of illness perceptions, as outlined in the Self‐Regulatory Model of illness, with depression among individuals diagnosed with lupus. Methods: A mail‐out questionnaire was completed by 154 members of the Australia Lupus Foundation and Lupus Foundation of New South Wales. Each questionnaire consisted of a Lupus Medical and Symptoms Questionnaire, the Illness Perceptions Questionnaire‐Revised and the Cardiac Depression Scale. Results: Hierarchical regression analysis revealed that individuals who reported a perception of their illness as having negative life consequences, an unpredictable nature and themselves possessing little understanding of lupus, reported high levels of depression. Conclusions: This study indicated the existence of a high level of depressive symptoms among individuals diagnosed with lupus, and reinforces the need for screening procedures in chronic illness, and treatment interventions that target maladaptive illness perceptions. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Clinical features of patients with myasthenia gravis associated with autoimmune diseases

We investigated the incidence and clinical features of patients with myasthenia gravis (MG) associated with autoimmune diseases. Associated autoimmune diseases were found in 28 of 142 consecutive Japanese MG patients (19.7%), amongst which Graves' disease (7.7%) and Hashimoto's thyroiditis (4.2%) were predominant. The clinical features of MG patients with Graves' disease were different from those of MG patients without autoimmune diseases in terms of age at onset of MG symptoms (35.5 ± 4.0 years and 49.0 ± 1.7 years; P  < 0.05), positivity for the anti-acetylcholine receptor antibody (44.4% and 89.8%; P  < 0.05), and association with thymic hyperplasia (72.7 and 17.9%; P  < 0.05). The therapeutic outcome of MG patients with Graves' disease and that of those without autoimmune diseases were not significantly different. Further studies should be performed to investigate whether MG associated with Graves' disease is a distinct subtype of MG.     

Two Autopsy Cases of Pick's Disease with Neurofibrillary Tangles

Abstract: Two cases of presenile dementia were presented. Both showed "stehende Redensarten" and aphasia. Histopathologically, besides Pick features–temporal lobe atrophy, fibrillary gliosis of the temporal white matter and neuronal loss in the 2–3 cortical layers–, Alzheimer features–neurofibrillary tangles and granulo-vacuolar degeneration–were found in both cases. But no senile plaques were found. Pseudocalcaerous deposits were observed in the cerebral cortex, basal ganglia and cerebellum. Atypical cases with both Pick's and Alzheimer's diseases in the literature were classified into four groups according to the extent of the features of each disease. Sensory aphasia, which is relatively unusual in Pick's disease, was correlated to the atrophy of left Tl, and similar cases in the literature were reviewed.     

地塞米松与甘露醇对急性重症脑血管病脑保护作用观察

目的分析使用地塞米松与甘露醇对急性重症脑血管病患者的脑保护作用,为提高患者的治疗效果提供参考。方法选择2011-08—2014-03我院收治的急性重症脑血管病患者60例为研究对象,随机分为2组。对照组使用甘露醇联合常规治疗,实验组给予常规治疗、甘露醇联合地塞米松治疗,观察2组治疗效果。结果实验组患者病死率更低,GCS评分优,与对照组患者比较差异有统计学意义(P0.05);2组并发症对比差异无统计学意义(P0.05)。结论地塞米松联合甘露醇对急性重症脑血管病患者的治疗效果更好,脑保护作用强,且安全性好。     

Lower motor neuron disease in a patient with hodgkin's disease treated with radiotherapy

A case of lower motor neuron disease after extended field irradiation for cervical stage I_A nodular sclerosing Hodgkin's disease is reported. Recurrence of Hodgkin's disease is excluded and other diagnostic possibilities are discussed. We compared this case with twenty-four similar cases reported in the literature after irradiation of the spinal cord for Hodgkin's disease or other neoplasms. Special features included the relatively advanced age of the patient, the long latency period, a premonitory CK-rise and reversibility. The entity is considered to be a very rare and relatively benign complication of spinal cord irradiation important to recognize as an entity in order to avoid extensive reevaluation.     

住院精神疾病患者合并躯体疾病调查

目的：了解住院精神疾病患者合并躯体疾病的种类和频度。方法：收集男、女各1个病房的全部患者142例,了解合并躯体疾病情况。结果：89．4％患者合并躯体疾病,常见的有心血管系统,内分泌系统,皮肤,消化系统,牙齿和呼吸系统疾患。结论：住院精神疾病患者躯体疾病种类多且常见,必需加以重视。