Fabry病合并心脏受累的诊治进展

Fabry病是由编码溶酶体水解酶α-半乳糖苷酶A的GLA基因突变引起的X染色体连锁隐性模式遗传的溶酶体贮积症.绝大多数Fabry病患者合并心脏受累,出现包括心肌肥厚、传导障碍、心律失常、瓣膜病变、心力衰竭等复杂并发症,其中心脏性猝死是Fabry病患者死亡的首要原因.生物标志物水平测定及基因检测是目前诊断Fabry病的主...     

Fabry病三例心脏表现

目的 增加心脏科医生对Fabry病患者的诊断意识.方法 入选2007年在我院诊治并初次确诊的3例不同家系的有心脏表现的Fabry病先证者,记录年龄、性别、病史、家族史、主要症状、心电图与心脏影像学表现.结果 3例患者均为女性,年龄为41～57岁,早年可有本病的典型症状,并有家族史.3例患者均因心脏症状就诊,心电图有ST-T改变,行心脏影像学检查提示左心窜壁肥厚.3例患者白细胞α半乳糖苷酶(α-GAL)水平均低于正常,例1的α-GAL水平最低,其心脏症状最为严重,出现心脏表现的年龄最轻,并伴有其他脏器的损伤.结论 Fabry病患者可因心脏症状与表现就诊,仔细询问家族史与早年症状,注意多脏器损伤的特点,有助于Fabry病患者的识别.     

以心肌肥厚为主要临床表现的法布里病母子案例分析

<正>法布里病(Fabry disease)是一种由GLA基因突变引起的X连锁溶酶体储存障碍,导致α- 半乳糖苷酶A活性缺乏,致使鞘糖脂在体液和全身细胞溶酶体中积累。出现皮肤、周围神经、肾脏、脑、眼、胃肠道及心血管等多器官系统的损害。其中,心脏受累的特征性表现为进行性心肌肥厚、心肌纤维化、心律失常和心力衰竭,称为Fabry心肌病,具有心脏猝死的潜在风险^[1]。本文报道以心肌肥厚为主要表现的法布里病母子病例,以提高对法布里病男女性发病的认识。     

一例Fabry病患者α-半乳糖苷酶基因突变和酶活性分析

目的 分析1例临床诊断的15岁典型Fabry病男性患者的临床表现、α-半乳糖苷酶A(α-GalA)基因(GLA)突变位点及其活性,并对无临床表现的患者母亲进行了相应的对照分析.方法 收集该例患者的临床资料,提取患者及其母亲、1名健康对照者的外周血基因组DNA,PCR分段扩增GLA基因的7个外显子,产物纯化后克隆入T载体进行DNA测序,检测是否存在突变位点,进一步应用荧光底物法榆测α-Gala的活性.结果 基因检测证实患者GLA基凶第7号外显子发生一个错义突变,即10036-10038位的AAG缺失(10036-10038delAAG),导致其编码的第374位的赖氨酸和第375位甘氨酸突变成精氨酸,该突变位点经国内外文献检索未见报道.该患者为带有突变基因的半合子,母亲为携带突变基因的杂合子,健康对照者未发现突变.α-GalA酶活性检测结果显示,携带该突变位点GLA基因的患者,其α-GalA酶活性只有健康对照者的50%左右,患者母亲的α-GalA酶活性为健康对照者的70%左右.结论 对临床疑似的Fabry病患者及其亲属,进行GLA基冈突变检测,结合α-GalA酶活性检测,有助于早期筛选出家系中的其他患者,能更加深入地了解Fabry病的分子发病机制.     

法布里病治疗新进展

法布里(Fabry)病是X连锁遗传的溶酶体贮积症,发病率为1∶47.6万～1∶11.7万,其中男性新生儿发病率约为1∶4万。Fabry病在儿童时就可发病,到中年可出现危及生命的并发症。男性半合子发病早,受累重,多死于终末期肾功能衰竭,女性杂合子多于中年伴发左心室肥大。研究显示,     

α-半乳糖苷酶A活性检测对Fabry病筛查和诊断的意义

测定100名体检者与1例Fabry病患者的外周血粒细胞和血浆中的d-半乳糖苷酶A(α-GalA)活性.结果显示,100名受试者外周血粒细胞与血浆中的α-GalA活性平均值分别为(51.97±15.24)nmol·h-1·mg-1和(148.08±26.30) nmol·h-1·ml-1;其血浆中α-Gal A活性与外周血粒细胞α-Gal A活性呈正相关(r=0.533,P＜0.01);Fabry病患者外周血粒细胞与血浆中α-Gal A活性分别为1.05 nmol· h-1·mg-1和10.06 nmol·h-1·ml-1,均明显低于所测定人群酶活性范围下限.提示血浆与外周血粒细胞α-GalA活性均可用于Fabry病的筛查和诊断.     

Fabry病一例报道并文献复习

目的：探讨Fabry 病的临床表现、诊断及鉴别诊断，提高临床医师对Fabry病的认识，降低漏诊率。方法：报道1例罕见的Fabry病肾损害，结合文献对该病的临床表现、诊断、鉴别诊断及治疗和预后进行探讨。结果：患者为中年男性，发病年龄为30岁，临床表现主要为肾脏损伤及周围神经病变，伴有尿毒症家族史，中性粒细胞测α-半乳糖苷酶示酶活性：0nmol/mg/hr，基因突变：p.H125T（c.373C>T），最终确诊Fabry病。患者曾至多家医院就诊，均未明确病因，漏诊率高。结论：Fabry病属于遗传性肾脏疾病，为临床罕见性疾病，容易漏诊，确诊需仔细的询问病史、肾脏病理检查、测定血清α-半乳糖苷酶水平及基因诊断。     

Fabry病及其酶替代疗法

Fabry病是X性连锁隐性遗传性疾病，又称α-半乳糖苷酶缺乏症，是由于先天性α-半乳糖苷酶A缺乏所致，属于溶酶体贮积病的一种。1898年由Anderson和Johann Fabry各报告1例故名AndersonFabry病，简称Fabry病。Fabry病特征性临床表现为弥漫性皮肤血管角质瘤和发作性肢体疼痛，本病后期常出现。肾脏、心脏和脑血管等器官的进行性损害。Fabry病近年之所以引起人们的关注，     

Fabry心肌病的诊断与治疗进展

法布里病（Fabry）是一种罕见的X染色体连锁遗传性疾病, 由于a-半乳糖苷酶A( alphagalactosidase A, GLA, 一种溶酶体酶)基因发生突变或缺失,引起体内GLA部分或全部缺乏,造成其代谢底物三己糖酰基鞘脂醇( globotriaosylceramide, Gb3)在人体各器官、组织蓄积,引起多个系统损害,其中心血管系统受累常见,主要表现为心肌肥厚、瓣膜损害、收缩/舒张功能减低,心律失常等,这些病变与患者心力衰竭、心源性猝死等密切相关。为了提高临床医生对Fabry病患者心脏受累表现的认识和诊治,本文将对Fabry 心肌病诊断与治疗的新进展作一综述。     

一个Fabry病家系的GLA基因突变分析

目的对一个临床诊断的非典型Fabry病患者进行α半乳糖苷酶基因(GLA)进行突变分析.方法抽取患者家系中4名成员的外周血基因组DNA,PCR分段扩增位于Xq22的GLA基因的7个外显子,产物纯化后直接进行DNA测序检测突变.结果测序显示,男性患者GLA基因的第6外显子存在CGA301CAA(Arg301Gln)突变,该患者为带有突变基因的半合子,母亲为携带突变基因的杂合子,哥哥及父亲为CGA301野生型的半合子.结论对临床诊断的Fabry病患者及其亲属,进行GLA基因突变检测可以进行基因诊断,并有助于早期筛选出家系中的其他患者.     

Joint manifestations of Fabry's disease

Summary We describe 2 patients with Fabry's disease with disabling crises of burning pain in hands and feet. These crises were accompanied by fever and an elevation of the erythrocyte sedimentation which often led to erroneous diagnosis of other rheumatic conditions. Fabry's disease should be considered on the different diagnoses of intermitent rheumatic syndromes.     

Cardiac involvement in Fabry's disease

Clinical Fabry's disease is due to any of multiple mutations in the X-linked alpha-galactosidase gene. These mutations are kindred-specific, often spontaneous, and produce varying degrees of functional enzyme deficiency resulting in deposits of specific glycosphingolipid (cerumide), especially in the vasculature, kidneys, heart and reticuloendothelial tissue. Disease frequency has probably been over-estimated at 1/40,000; so few centres have developed clinical experience of the disease, though the disease has been identified in all major racial groups.     

Vestibular and cochlear manifestations in Fabry's disease

Anderson-Fabry's disease corresponds to an inherited disorder transmitted by an X-linked recessive gene. The disease is caused by an alpha-galactosidase deficiency leading to an abnormal glycosphingolipid metabolism, resulting in glycosphingolipids deposits all over the body. The disease affects all organs over the body and can be responsible for central nervous system or renal failure, heart attack, which can lead for early death in absence of diagnosis and treatment. In addition to these life-threatening manifestations, other problems which may have a profound impact on quality of life, such as hearing loss, have been relatively neglected. Thus, a large proportion of patients with Fabry's disease suffer from sensorineural hearing loss, with both progressive hearing impairment and sudden deafness, and peripheral vestibular deficits with dizziness and vertigo. The exact pathophysiologic mechanism(s) of those otological complications is still studied, but both cochleo-vestibular disorder and vascular origin seems to be involved. For many years, only symptomatic treatment has been available. For the past ten years, the introduction of enzyme replacement therapy with recombinant agalsidase-α or -β provides new prospect for these patients, decreasing the risk of complications. Still on study, it may also be active both on hearing loss and vestibular disturbances.     

Cardiac manifestation of Fabry's disease: current knowledge

Fabry's disease is a rare lysosomal storage disease caused by the X-linked defect of the enzyme alpha-galactosidase A leading to the intracellular accumulation of glycosphingolipids in various organs and tissues. Cardiac involvement is frequent and, in individuals with some residual enzyme activity, may be the sole manifestation of the disease. Hemizygous men are generally more seriously affected than heterozygous women. The dominant cardiac manifestations include myocardial hypertrophy of the left ventricle, which, in some patients, mimics hypertrophic cardiomypathy. Left ventricular systolic function is usually preserved, on the other hand mild to moderate diastolic dysfunction is regularly detected. Valvular abnormalities are frequently noted. However, hemodynamically significant lesions are rare. Conduction system involvement leads initially to the shortening of atrioventricular conduction, in later stages, with a progression of the disease, antrioventricular blocks and various forms of supraventricular and ventricular arrhythmias appear. Myocardial ischemia in Fabry disease has in most cases a functional origin due to endothelial dysfunction of coronary arteries and also due to the increase oxygen demand of hypertrophied myocardium. The results of so far performed studies with enzyme replacement therapy are promising in preventing further deterioration and even improving function of affected organs.     

Cardiac abnormalities in Anderson-Fabry disease and Fabry's cardiomyopathy

Fabry's disease is an X-linked lysosomal storage disease most often associated with renal dysfunction and death due to renal failure in patients' fourth and fifth decades of life. However, cardiac manifestations including arrhythmias, angina and heart failure are common and probably underrecognized. Furthermore, Fabry's disease is now recognised as also affecting female carriers, who manifest signs later than males. A variant of Fabry's has been identified that only affects cardiac tissue, which presents as an unexplained hypertrophy of the left ventricle in middle-aged patients, possibly with women more affected than men. Given that epidemiological studies report a prevalence of Fabry's cardiomyopathy among middle-aged patients with cardiac hypertrophy to be anywhere from one to 12%, it is reasonable to screen these patients for alpha-galactosidase A deficiency. Although mortality data is lacking from randomised, controlled trials of galactosidase replacement therapy, there are some reports of improvement in cardiac endpoints. Therefore patients with known Fabry's disease should be screened early for cardiac involvement, as treatment benefit may not be seen once cardiac fibrosis has developed.     

Cardiac manifestations of Lyme disease

Three cases of Lyme's disease with cardiac involvement are reported. One patient had myocarditis complicated by symptomatic complete AV block and two patients had asymptomatic 1st degree AV block. There were no abnormalities on echocardiography. The cardiac changes occurred between the 18th and 40th day after the onset of the disease and persisted 10 days: however these conduction defects may vary within a few hours. A rapid and complete cure was obtained with antibiotic therapy.