X连锁无丙种球蛋白血症的临床特点

目的 探讨中国X连锁无丙种球蛋白血症(XLA)的临床表现和实验室检查特点。方法 本组8例,经流式细胞仪检测Bruton′s酪氨酸激酶(BTK)表达和(或)基因分析诊断为XLA,总结其临床表现,并对其免疫功能进行评价。结果 本组8例,均为男性。发病年龄3个月～3岁,诊断为XLA时平均年龄6岁。8例患儿都有反复急性上呼吸道感染和肺炎伴发热,上呼吸道感染主要为鼻咽部感染,仅1例曾患中耳炎。反复多关节炎较多见(3/8),没有关节感染的证据。仅2例母系家族中的男性有类似疾病史。诊断时均表现为营养不良和生长发育延迟。周围淋巴组织发育不良,扁桃体和淋巴结很小或难以查及。实验室检查血清Ig和循环B细胞明显降低。6例CIM/CD8比值明显倒置。结论 本组中国XLA患儿诊断时年龄较大,临床表现以反复呼吸道感染、肺炎为主,多关节炎发生率较高,家族史不明显。大部分患儿存在CD4/CD8比值明显倒置,原因和意义尚不清楚。     

X连锁无丙种球蛋白血症的基因诊断

目的研究我国X连锁无丙种球蛋白血症(XLA)患者Bruton’s酪氨酸激酶(BTK)基因的突变类型。方法采用逆转录-聚合酶链反应(RT—PCR),获得7例XLA患者cDNA。使用8对不同引物分2步扩增BTK cDNA,PCR产物测序。突变结果通过对DNA外显子相应部位扩增、测序证实。对其中4例母亲进行基因分析。结果7例患者的基因突变均位于BTK基因的编码区,3例在BTK的血小板-白细胞C激酶底物同源区,2例位于酪氨酸激酶区,其他2例分别位于Src同源区2和Src同源区3。突变包括：错义突变、无义突变、重复序列和片段缺失。除错义突变引起单一BTK氨基酸改变外,突变还分别造成终止密码子形成和阅读框架移位。其中4例为未见报道的新突变。进行基因分析的4例母亲中,3例为携带者。结论本组患者临床表现为典型XLA,检测出的7种突变均位于BTK基因编码区,其中4种是未见报道的新突变。XLA可以通过基因分析进行确诊以区别与其他低丙种球蛋白血症。     

X-连锁无丙种球蛋白血症临床分析及基因诊断

目的分析X-连锁无丙种球蛋白血症(XLA)的临床特点及Bruton酪氨酸激酶(BTK)的基因突变情况。方法回顾分析通过基因检测确诊的20例XLA患儿的临床资料,以及采用Sanger测序方法分析BTK基因的突变情况。结果 20例患儿均为男性,发病年龄6～54月龄,平均(26.3±14.61)月龄;基因诊断确诊年龄26～168月龄,平均(64.7±38.22)月龄;诊断周期中位数为27.5月龄(3～114月龄)。临床表现以呼吸道感染为主,其中18例诊断为肺炎,另外2例为消化道感染。免疫功能检测示成熟B淋巴细胞缺如或比例显著降低,血清IgG、IgA及IgM水平明显降低。基因检测提示错义突变10例,无义突变4例,移码突变3例,内含子剪切位点突变2例,剪接突变1例。20例患儿明确诊断后均给予静脉输注丙种球蛋白替代治疗,感染频次均显著减少,均无后遗症。结论对反复严重、特殊部位感染的男童,尤其是有相关家族史的患儿,尽早行免疫功能筛查,并行基因检测明确诊断及遗传咨询。     

17例X连锁无丙种球蛋白血症临床表型分析

目的：分析17例单中心临床诊断的X连锁无丙种球蛋白血症（X-linked agammaglobulinemia, XLA）的临床表型特点。方法：2000年1月至2007年4月北京儿童医院住院患儿,根据临床反复感染表现、血IgG<2g/L、外周血成熟B淋巴细胞缺失或明显降低（<1%）诊断为XLA者,分析临床特点,总结规律。结果：首次诊断年龄平均为7.7岁,88.2%患儿首次诊断年龄>6岁。首次出现症状年龄平均为4.2岁,11.8%患儿首次出现症状年龄<1岁,17.6%患儿首次出现症状年龄为1~2岁。64.7%患儿首发症状为呼吸系统感染,大部分患儿均以此为主诉入院。35.3%患儿有关节炎表现。皮肤及软组织感染少见于<1岁年龄组。大年龄组患儿可出现突发败血症和/或深位部感染。结论：该组患儿发病年龄及首次诊断年龄均较迟,呼吸系统感染为最常见的主诉,关节炎的比例较高。>1/2的患儿血CD4+T细胞减少,CD8+T细胞增加,CD4/CD8比例倒置,NK细胞减少。     

11例X-连锁无丙种球蛋白血症临床特点分析

目的 总结X-连锁无丙种球蛋白血症(X-linked agammaglobulinemia,XLA)患儿的临床特点,提高对本病的早期诊断率.方法 回顾性分析2003年12月至2011年11月中国医科大学附属盛京医院住院的11例XLA患儿的临床资料,分析XLA的临床特点.结果 11例XLA患儿首次出现症状年龄最早为0.4岁,最迟为4岁,平均2.4岁;初次诊断年龄3.5～13.0岁,平均7.0岁;63.6％(7/11)的患儿首次诊断年龄＞7岁;母系家族中男性有类似疾病史的患儿仅占18.2％ (2/11);2例因重症感染死亡,1例失访,其余8例均存活.11例(100％)患儿有呼吸道感染史,中耳炎及消化道感染率分别为54.5％ (6/11)和36.4％(4/11).11例患儿血IgA、IgM、IgG较正常值均明显减低;其中9例血IgG均＜2g/L,其余2例血lgG均＜2.4 g/L.外周血CD19均≤1％,T细胞的突出表现为其中9例CD4/CD8比值倒置.11例患儿中8例经基因检测确诊为XLA.结论 XLA患儿发病年龄相对较早,初诊年龄相对较晚;感染主要以呼吸系统为主,中耳炎及消化道感染亦较为常见,未见有关节炎表现;有明确家族史者甚少;早期诊断、静脉注射人丙种球蛋白长期维持治疗可改善预后.     

X连锁无丙种球蛋白血症

X连锁无丙种球蛋白血症是最早发现的人类原发性免疫缺陷病,为X连锁隐性遗传病,其缺陷基因Btk的突变主要影响B细胞的成熟,导致患儿体液免疫功能障碍。临床以反复化脓菌感染为主要表现,除肠道病毒外对其他病毒的感染过程反应正常。实验室检查发现外周血B细胞数量明显降低,缺乏各类免疫球蛋白。目前主要采用丙种球蛋白替代治疗,随着基因技术的不断发展,有望利用基因治疗达到根治目的。     

X-连锁无丙种球蛋白血症患儿临床表型和基因诊断分析

目的分析3例X-连锁无丙种球蛋白血症(X-linked agammaglobulinemia,XLA)的临床表型特点及Bruton’s酪氨酸激酶(BTK)基因变异情况,以提高临床医师对XLA的认识。方法收集本组3例XLA患儿外周静脉血,测定其血清Ig水平和淋巴细胞亚群表达情况,采用RT-PCR和测序的方法分析患儿及母亲BTK基因变异情况,并总结其临床特征。结果在临床特征方面3例均为男性患儿,诊断XLA时的年龄分别为4岁、12岁6个月和2岁2个月,平均诊断年龄6岁3个月。3例患儿临床均表现为反复感染,如患中耳炎、鼻窦炎、反复全身脓疱疹、脓胸、细菌性关节炎、细菌性脑膜炎等,3例诊断时均表现为营养、生长发育较差,周围淋巴组织发育不良,扁桃体和淋巴结很小或难以查及;实验室检查血清Ig和循环B淋巴细胞明显降低;在基因诊断方面3例均发现存在BTK基因突变,例1为外显子9的949位G缺失,例2为外显子17的错义突变,例3为外显子15的错义突变,对例2、例3患儿母亲进行BTK基因分析,发现均为携带者,存在相同的基因突变。结论本组3例中国贵州籍XLA患儿诊断时年龄较大,临床主要表现为不同部位的反复化脓性细菌感染,在临床表现基础上通过BTK基因分析有助于XLA患儿的进一步明确诊断,并且有利于发现携带者和进行遗传咨询。     

X连锁无丙种球蛋白血症的分子生物学研究进展

X连锁无丙种球蛋白血症是最早发现的人类原发性免疫缺陷病，其缺陷基因定位于X染色体长臂中部（Xq21.3-22)，并已经被成为克隆，所编码的蛋白为细胞浆性蛋白酷氨酸激酶，可通过多条细胞信号传导通路对B细胞的发育及功能性反应产生双重作用，该基因突变的结局可导致外周血成熟B细胞数显著降低，临床上产生相应的表现，本文就此症近年来的研究进展作一扼要介绍。     

X-连锁低丙种球蛋白血症一例

患儿男 ,5岁 ,因“左膝关节肿痛半年”入院。半年前患儿出现左膝关节疼痛 ,不肿 ,影响活动 ,夜间疼痛重 ,不伴有发热、皮疹及其他关节疼痛。 4个月前左膝关节轻微肿胀 ,外院诊为“关节炎” ,未正规治疗。 2个月前左膝关节肿胀明显加重 ,影响行走及下蹲 ,来我院就诊。患儿为第 8胎第 3产出生 ,患儿母亲第 1,2胎于孕 2个月自然流产 ;第 3胎女 ,孕 7个月因羊水多、胎儿畸形引产 ;第 4胎为足月 ,正常分娩出生 ,女孩 ,15岁 ,健康 ;第 5胎男 ,1岁 4个月 ,因发热给予臀部肌肉注射后 ,出现局部感染脓肿 ,发展为“败血症” ,“胸膜炎” ,“化脓性脑膜…     

流式细胞技术在诊断X-连锁无丙种球蛋白血症的应用

目的：探讨流式细胞技术在诊断X-连锁无丙种球蛋白血症(XLA)中的应用。方法：采用流式细胞术检测白细胞分化抗原19(CD19),统计循环B细胞数量,从而使XLA的临床诊断更可靠。结果：8例IgG<2 g/L 的男性患儿中5例(62.5%)CD19<1%而确诊为XLA者。结论：应用流式细胞术检测CD19可提高诊断XLA的准确率。     

X-linked agammaglobulinemia: clinical and immunologic evaluation of six patients

The clinical and immunologic features of six patients with X-linked agammaglobulinemia (XLA) are presented. The most common presenting manifestations were respiratory and gastrointestinal tract infections. On admittance to the hospital, one patient had a history of recurrent meningitis, another had a dermatomyositis-like syndrome, and still another had a history of recurrent arthritis.     

Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients

Background

X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton’s tyrosine kinase (BTK) gene mutation. XLA patients have an extremely small amount of peripheral B cells and profound deficiency in all immunoglobulin isotypes. We analyzed the clinical, immunologic, and molecular characteristics of children with XLA in an attempt to improve the diagnosis and treatment of XLA in China.

Methods

Twenty children with XLA-compatible phenotypes from 18 unrelated families were enrolled in this study. The BTK gene was amplified and sequenced, followed by mutation analysis in these children and their female relatives.

Results

Eighteen different mutations of the BTK gene were identified in the 20 patients. Eleven mutations had been reported previously including eight missense mutations (c.994C>T, c.1987C>A, c.1885G>T, c.502T>C, c.1085C>T, c.1816C>T, c.214C>T, c.1912G>A) and three nonsense mutations (c.1267T>A, c.1793C>G, c.1618C>T). Seven novel mutations of the BTK gene were also presented and included five missense mutations (c.134T>A, c.1646T>A, c.1829C>G, c.711G>T, c.1235G>A), one splice-site mutation (c.523+1G>A) and one insertion mutation (c.1024-1025in sTTGCTAAAGCAACTGCTAAAGCAAG). Eight out of 18 mutations of the BTK gene were located in the TK domain, 4 in the PH domain, 4 in the SH2 domain and 2 in the TH domain. Genetic study for carrier status was carried out in 18 families with definite BTK gene mutations. Nine carriers with BTK gene mutations were identified. Six families without carriers were detected, and 3 patients were not tested in this study.

Conclusion

Our results support that molecular genetic testing represents an important tool for early confirmed diagnosis of congenital agammaglobulinemia and may allow accurate carrier detection and prenatal diagnosis.     

X-linked agammaglobulinemia and isolated growth hormone deficiency

X-linked agammaglobulinemia and isolated growth hormone deficiency was first described in 1980 and then classified as a different primary immune deficiency. Delayed puberty in patients with X-linked agammaglobulinemia may result in delayed secretion of growth hormone (GH). To determine true isolated growth hormone deficiency. GH stimulation tests and other hypophyseal hormone evaluations must be performed. In this paper, we report a 15-year-old boy with X-linked agammaglobulinemia and isolated growth hormone deficiency, and review related literature.     

X-linked agammaglobulinemia complicated with endobronchial tuberculosis

Aim: We report a case of X‐linked agammaglobulinemia complicated with endobronchial tuberculosis. Methods: We observed the patient’s clinical course and analysed his data retrospectively. Results: Interestingly, the T‐cell proliferation activity in this patient was intact, and the CD4‐positive T cells produced interferon gamma. However, the result of the quantiferon alpha‐2b test was negative. Conclusion: The findings of this case suggest that the quantiferon alpha‐2b test may not be diagnostic for tuberculosis not only in patients with T‐cell disorders but also in cases with B‐cell deficiencies such as X‐linked agammaglobulinemia.     

Carrier detection in typical and atypical X-linked agammaglobulinemia

We have recently demonstrated that B cells from obligate carriers of typical X-linked agammaglobulinemia (XLA) exhibit nonrandom X chromosome inactivation. The active X is always the X that does not carry the gene defect. To determine if this were also true in carriers of atypical XLA and to provide carrier detection for all women at risk of being carriers of XLA, we developed a technique that permits analysis of X chromosome inactivation in cells from any woman. This technique combines the production of somatic cell hybrids that selectively retain the active X chromosome with the use of X-linked restriction fragment length polymorphisms that permit the distinction of the two X chromosomes. Three obligate carriers of typical XLA and four women whose sons might be considered to have atypical or sporadic XLA were studied. B cell hybrids from all seven women demonstrated exclusive use a single X as the active X. In addition, B cell hybrids from four of eight women at 25% or 50% risk of being carriers exhibited nonrandom X chromosome inactivation, indicating that these women were also carriers of X-linked forms of hypogammaglobulinemia. These results illustrate a technique that can be used both to help define XLA and to provide carrier detection for all women at risk of being carriers of this disorder.