Fevers and mouth ulcers

Mouth ulcers are commonly caused by infection but may be due to neutropenia. The most common form of hyper-IgM syndrome is of X-linked inheritance and caused by CD40 ligand gene mutations. Consider hyper-IgM syndrome in a male child with recurrent bacterial or opportunistic infections, neutropenia, hypogammaglobulinaemia (IgG and IgA) and normal T- and B-cell counts. In X-linked hyper-IgM syndrome: - the serum IgM concentration is normal in about 50% of cases. - transient or persistent neutropenia occurs in 70% of cases. First-line therapeutic options for hyper-IgM syndrome include regular intravenous immunoglobulin and prophylactic trimethoprimsulphamethoxazole.     

川崎病患儿CD4+T淋巴细胞表面CD40L表达及其与冠状动脉损伤的关系

目的通过检测川崎病(KD)患儿静脉输注入血丙种球蛋白(丙球)治疗前后外周血T细胞表面CD40L(CD154)表达,探讨KD冠状动脉损伤的发病机制。方法采用流式细胞仪检测26例KD患儿静脉输注丙球治疗前后、16例其他发热性疾病患儿、15例正常儿童外局血T细胞表面的CD40L表达。采用酶联免疫吸附试验检测相应血清中E-选择素。结果KD患儿CD4 T细胞表面CD40L表达及血清E-选择素显著高于其他发热性疾病组及正常对照组(P<0.01),KD患儿静脉输注丙球治疗后明显下降(P<0.01)。CD4 T细胞表面CD40L表达及E-选择素与KD冠状动脉损伤有关,而CD8 T细胞表面CD40L的表达与冠状动脉损伤无关。KD患儿CD4 T细胞表面CD40L表达与E-选择素水平正相关(r=0.626P<0.05)。结论CD40L异常表达及血清E-选择素在KD发病机制中起重要作用。静脉输注丙球能下调CD40L表达及血清E-选择索,有利于血管炎治疗。     

The hyper IgM syndrome--an evolving story

The hyper IgM syndromes (HIGM) are a group of primary immune deficiency disorders characterized by defective CD40 signaling by B cells affecting class switch recombination and somatic hypermutation. As a consequence, patients with HIGM have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections. The most common HIGM syndrome is X-linked and due to mutations of CD40 ligand (CD40L) expressed by activated CD4(+) T lymphocytes. Four other genes, expressed by B cells, have been associated with the HIGM phenotype. Mutations of CD40, the receptor for CD40L, cause a rare autosomal form of HIGM with a clinical phenotype similar to CD40L deficiency. Mutations of Activation-Induced Cytidine Deaminase (AICDA) and Uracil (DNA) Glycosylase (UNG), both expressed by follicular B lymphocytes, lead to defective class switch recombination and somatic hypermutation. Mutations of Nuclear Factor kappa B Essential Modulator (NEMO), an X-chromosome associated gene, result in hypohidrotic ectodermal dysplasia and immune deficiency. Thus, the molecular definition of these rare primary immune deficiency disorders has shed light on the complex events leading to the production of high-affinity, antigen-specific antibodies of different isotypes.     

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature

Hyper-IgM syndromes are characterized by normal or elevated serum IgM levels with the absence or reduced levels of other immunoglobulins. There are some patients with defective class-switch recombination (CSR) who do not have CD40L, CD40, AID, and UNG defects. The aim of this study is to determine the B-cell functions of patients with Hyper-IgM type 4 phenotype. Ten patients (seven males and three females) 84.2 ± 16.5 months of age with initial low serum IgG and IgA and high or normal IgM levels were included. Clinically, 50% had recurrent upper respiratory tract, 10% urinary tract, 10% lower respiratory tract infections, and 30% had mixed type infections. Lymphoid hyperplasia, overt autoimmune manifestations, or malignancy was not noted. Seven of 10 patients were studied twice; at the age of 34.2 ± 13.7 and at 86.6 ± 12.3 months. Absolute lymphocyte counts and lymphocyte subsets were normal in all cases. All of them had normal expression of CD40 on B cells and CD40L on activated T cells for males. At first examination, all patients had normal in vitro sCD40L+rIL-4-induced B cell proliferation response and somatic hypermutation but CSR towards IgE was absent. AID and UNG genes did not show any abnormalities. All showed improvement in both clinical findings and Ig levels during the follow-up period of 55.8 ± 14.8 months. Ages for normalization of IgG and IgA were 68.2 ± 8.7 and 70.2 ± 21.6 months, respectively. During the second evaluation: In vitro sCD40L+rIL-4-induced B-cell proliferation was normal in all cases, whereas CSR was still abnormal in five of eight patients. Two of the patients had an increase in in vitro CSR response but still low IgG2 subclass levels. Three patients with initially absent in vitro CSR response also normalized. Conclusion: Clinical manifestations and immunoglobulin levels of the patients with Hyper-IgM type 4 phenotype recovered in late childhood at about 6 years of age. There was a transient CSR defect which was not observed in cases with transient hypogammaglobulinemia of infancy. Detection of a non-AID or non-UNG associated CSR defect in infancy should be confirmed later on since spontaneous recovery may occur.     

The expression of CD40 on monocytes of children with primary humoral immunodeficiencies

The interactions between CD40 and CD40L (CD154) are critical for effective humoral immune response. CD40 signaling facilitates T lymphocyte dependent B cell proliferation and immunoglobulin isotype switch. The objective of our study was to investigate the CD40 and CD40L expression on peripheral blood mononuclear cells (PBMC) of children with symptomatic transient hypogammaglobulinemia (THI), common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD). Additionally we studied the production of IL-12 and IL-18 by PBMC stimulated with soluble CD40L. CD40 expression was analyzed on B cells and monocytes, CD40L on activated T lymphocytes, using flow cytometry following staining of the cells with appropriate MAb. We found that CD40 expression on B cells and CD40L on activated T cells were essentially similar in the control and patient groups, while the decreased CD40 expression on monocytes was observed in THI and SIgAD patients compared with normal subjects. The most significant decrease of CD40 expression was observed in THI (37% of positive cells) in comparison with control (81% of positive cells). IL-12, but not IL-18, release by PBMC was increased in THI and CVID, but not in SIgAD. In conclusion we suggest that the decreased expression of CD40 on monocytes of children with THI and SIgAD, but not CVID, may be involved in the pathomechanism of these immunodeficiencies.     

过敏性紫癜外周血单个核细胞CD40 L表达及其干预研究

目的 观察过敏性紫癜患儿外周血单个细胞表达ＣＤ４０配体及其干预因素,以期探讨在过敏性紫癜发病机制中的作用并指导临床治疗。方法 用流工细胞技术,ＥＬＩＳＡ法及单向免疫扩散法检测观察组３３例患儿ＣＤ４０ Ｌ阳性细胞率,ＩＬ－４,ＩＬ－５及ＩｇＥ,Ａ,Ｇ,Ｍ,并与对照组比较。     

支气管肺炎患儿免疫功能变化的临床分析

目的：通过检测普通和重症支气管肺炎患儿血清补体、免疫球蛋白、淋巴细胞亚群变化,探讨免疫功能检测在支气管肺炎中可能的作用。方法：纳入符合诊断标准的普通和重症支气管肺炎患儿各20例,同时选取健康儿童20例为对照组。采用免疫速率散射比浊法和六色流式细胞仪分析法检测各组儿童血清IgA、IgG、IgM、补体C3、C4及淋巴细胞亚群CD3+、CD4+、CD8+、CD16+CD56+及CD19+指标变化。结果：普通及重症肺炎组IgA水平均较对照组明显降低（P0.05）;重症肺炎组CD4+、CD3+水平均较对照组降低（P0.05）。结论：支气管肺炎患儿存在免疫功能的紊乱,在重症组更为明显,免疫水平的变化与肺炎病情的严重程度相关。支气管肺炎患儿免疫功能检测具有重要的临床意义。     

X-linked severe combined immunodeficiency (X-SCID) with high blood levels of immunoglobulins and <Emphasis Type="Italic">Aspergillus</Emphasis> pneumonia successfully treated with micafangin followed by unrelated cord blood stem cell transplantation

In this report, we describe a patient with X-linked severe combined immunodeficiency (X-SCID) who had high serum IgG, IgA, and IgM levels. The boy did well until 6 months of age, when he developed interstitial pneumonia caused by Aspergillus species, with a white cell count of 12,840/μL and only 10% lymphocytes; IgG, 991 mg/dL; IgA, 65 mg/dL; IgM, 472 mg/dL. Cell markers showed only 6.3% CD3, 2.1% CD4, 0.7% CD8, but 92% CD19 and 0.1% CD16+CD56+ (NK cells). A mutation was detected within exon 2 (C196 A→C), leading to the substitution of proline for glutamine, which has not been reported previously. The boy was successfully treated with the new antifungal drug, micafangin (MCFG), at 5 mg/kg/day for 89 days. After resolution of the pneumonia, the patient underwent successful hematopoietic stem cell transplantation with completely matched unrelated female cord blood. The CD34 stem cell dose was 3.4×10⁴ cells/kg. In conclusion, MCFG can be a first line agent for Aspergillus pneumonia in immunocompromised hosts.     

X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa

Background

The objective of this study was to describe the clinical and molecular features of the first South African family with X-linked hyper-IgM syndrome (HIGM1).

Methods

Diagnoses were based on immunoglobulin results and the absence of CD40 ligand (CD40L) expression on activated T-cells. Complete molecular characterisation involved CD40L cDNA sequencing, and genomic DNA analysis by polymerase chain reaction amplification, restriction enzyme digestion and sequencing. A PCR-based diagnostic assay was established for carrier detection and prenatal diagnosis in this family.

Results

There were originally six children, three males and three females. The eldest boy died after being diagnosed with hypogammaglobulinaemia, before HIGM1 was considered. This disorder was diagnosed in the second eldest boy at the age of 5 years, after failing to detect CD40L expression on his activated T-cells. A deficiency of CD40L was also confirmed in the youngest male at the age of 5 years. Both younger brothers have since died of infections relating to HIGM1. Molecular investigation showed that exon 3 was deleted from the CD40L mRNA of the affected males. Genomic DNA analysis identified a 1.5 kilobase deletion, spanning exon 3 and including extended flanking intronic sequence. Carrier status in the mother was confirmed by RT-PCR of her CD40L mRNA. Genetic analysis of the three female children was deferred because they were below the legal consenting age of 18 years. A PCR-based assay for genomic DNA was established for easy identification of female carriers and affected males in the future.

Conclusions

This study confirmed the diagnosis of HIGM1 in the first South African family to be investigated and identified a novel mutation in the CD40L gene.

     

支气管哮喘患儿T细胞亚群和免疫球蛋白变化

目的　探讨外周血T细胞亚群和血清免疫球蛋白的改变在儿童支气管哮喘发病中的作用。方法应用酶联免疫吸附试验 ,SPA直接花环法及单向免疫扩散法对 30例支气管哮喘患儿和 2 0例健康对照小儿的外周血T细胞亚群和血清免疫球蛋白进行测定。结果　对照组CD3 + ,CD4 + 和CD8+ 的百分值分别为 72 .38± 8.19% ,45 .48± 4.2 7% ,31.2 9± 4.0 2 % ,CD4 + /CD8+ 比值为 1.2 8± 0 .2 3。哮喘患儿外周血CD3 + (37.15± 7.16 % )和CD8+(2 6 .5 6± 2 .18% )细胞数明显低于对照组 (P <0 .0 1) ,CD4 + (46 .10± 4.5 2 % )细胞数略高于对照组 ,差异无显著性(P >0 .0 5 ) ,CD4 + /CD8+ (1.5 1± 0 .44 )比值则显著高于对照组 (P <0 .0 5 ) ,对照组IgG ,IgA ,IgM ,IgE分别为10 .6 7± 2 .5 3g/L ,1.18± 0 .6 9g/L ,1.6 0± 0 .5 4g/L ,178± 30IU ;哮喘患儿血清IgE(386± 15 4IU)明显增高 (P <0 .0 1) ,IgM(1.2 9± 0 .41% ) ,IgG(9.35± 2 .2 6 g/L)则显著低于对照组 (P <0 .0 1,P <0 .0 5 ) ,IgA(1.34± 0 .76 g/L)两组差异无显著性 (P >0 .0 5 )。结论　哮喘患儿存在血清免疫球蛋白改变 ;T抑制细胞数量和 (或 )功能不足可能是导致免疫球蛋白改变的主要机制。     

儿童肺炎支原体肺炎免疫功能、降钙素原及C-反应蛋白变化及意义

目的 检测肺炎支原体肺炎（mycoplasma pneumoniae pneumonia,MPP）患儿免疫球蛋白、CD4＋T、CD8＋T、血清降钙素原（PCT）和C-反应蛋白（CRP）的水平,探讨其改变及临床意义.方法 收集2012年11月至2013年10月诊断为MPP的患儿126例,分为大叶性肺炎组（42例）及支气管肺炎组（84例）,以同时期儿科门诊体检的健康儿童28例为正常对照组,分别测定免疫球蛋白、PCT和CRP.结果 （1）MPP患儿IgG、IgM、IgE异常率高于正常对照组（P＜0.05）,IgA异常率无明显差异（P＞0.05）;大叶性肺炎组IgG异常率高于支气管肺炎组（P＜0.05）,IgM、IgE及IgA异常率无明显差异.（2） MPP患儿CD4＋T、CD4＋ T/CD8＋T比值较正常对照组明显降低（P＜0.05）.（3）MPP患儿血清PCT及CRP水平较正常对照组明显升高（P＜0.05）.结论 MPP患儿体液免疫与细胞免疫功能紊乱在MPP发病过程中起重要作用,且病情越重,免疫功能紊乱越明显,PCT、CRP对MPP病情评估有临床指导意义.     

儿童难治性肺炎支原体肺炎常规免疫指标的年龄依赖性变化分析

目的　通过控制年龄因素,探讨难治性肺炎支原体肺炎（RMPP）常规免疫指标变化。方法　回顾性分析2016年1月至2019年12月复旦大学附属儿科医院住院的120例MPP患儿的常规免疫指标。参考中国不同年龄及性别的健康儿童的外周血淋巴细胞亚群的参考值,将120例患儿分为正常或异常组,对于异常组的患儿进一步分为减少组或增多组。比较普通型肺炎支原体肺炎（GMPP）与RMPP两组患儿常规免疫指标的变化的差异性。 结果　RMPP组淋巴细胞亚群异常的患儿比例均高于GMPP组, 两组CD3+, CD19+及NK细胞百分比的差异具有统计学意义（P＜0.05）。两组多数患儿均表现为淋巴细胞计数、 CD3+、 CD4+、 CD8+及NK细胞绝对计数减少。进一步对淋巴细胞减少的亚群分析, 发现两组CD3+及NK细胞计数、 CD3+及NK细胞百分比、 CD4+百分比、 CD4+/CD8+差异具有统计学意义（P＜0.05）。各组血清免疫球蛋白（IgA、 IgM、 IgG、 IgE）水平差异无统计学意义（P＞0.05）。 结论　T细胞及NK细胞在MPP炎性反应中发挥重要作用, CD4+ 细胞及NK细胞与MPP的严重程度相关, 可能是RMPP的免疫致病机制之一。     

肺炎支原体肺炎患儿免疫发病机制及临床分析

目的　探讨肺炎支原体 (MP)肺炎免疫发病机制及其临床特点。方法　对 6 5 6例有呼吸道感染的患儿进行血清抗MP IgM和咽拭子MP DNA PCR检测 ,同时对 5 9例肺炎患儿进行血清IgG、IgM、总补体活性(CH50 )、补体C3 和循环免疫复合物 (CIC)测定。结果　MP肺炎组CIC阳性率为 4 8.5 % (16 / 33) ;非MP肺炎组阳性率为 11.5 % (3/ 2 6 ) ,前者明显高于后者 ,差异有显著性 (P <0 .0 1) ;MP肺炎组血清IgG、IgM浓度高于非MP组 ,两组差异显著 (P <0 .0 5 ) ;而CH50 、补体C3 则明显低于对照组 (P均 <0 .0 5 )。结论　免疫复合物介导损伤与MP肺炎的发病有关。     

新生儿感染性肺炎的临床和免疫功能研究

目的　探讨新生儿感染性肺炎的病因学、临床特征和免疫功能的变化。方法　采用酶联免疫吸附试验 (ELISA)检测 111例肺炎患儿血中 8型常见病毒及肺炎支原体特异性IgM ,速率散射比浊法测定C 反应蛋白 (CRP)和免疫球蛋白 (IgG及其亚类、IgA、IgM ) ,链菌素亲生物素 过氧化酶连接法 (SP)检测T淋巴细胞亚群 ,并对临床表现和其他实验室检查结果进行分析。选取同期非肺炎新生儿 30例作为对照。结果　⑴肺炎组 111例患儿血清中 ,特异性IgM阳性 4 0例 (36 0 % ) ;对照组 30例的血清中 ,特异性IgM检测均阴性。病毒及支原体感染 2 3例 (2 0 7% ) ,细菌感染 4 5例(40 5 % ) ,病毒及支原体与细菌混合感染 17例 (15 3% ) ,其他不明病原感染 2 6例 (2 3 4 % )。⑵新生儿感染性肺炎最常见的症状和体征是气促、发绀 ,其次是咳嗽、呛奶、肺部音、三凹征 ;X线检查以纹理模糊、纹理增多增粗、斑片影多见。⑶免疫学检查中 ,肺炎组CD3 、CD4细胞数小于对照组 (P <0 0 5 ) ,IgA、IgM含量大于对照组 (P <0 0 5 )。病毒及支原体感染组IgA含量大于其他不明病原感染组和对照组 (P <0 0 5 ) ;细菌感染组IgM含量大于对照组 (P <0 0 5 )。CD8、CD4/CD8、IgG、IgG1 4在肺炎组与对照组、各感染组两两间、各感染组与对照组之间     

支原体肺炎患儿辅助性T淋巴细胞亚群TH1、TH2细胞状况

目的　探讨肺炎支原体肺炎急性期患儿外周血淋巴细胞亚群以及辅助性T淋巴细胞亚群TH1、TH2细胞的改变 ,为免疫治疗的可能性提供依据。方法　采用流式细胞仪技术 (FACS)检测了3 5例支原体肺炎急性期患儿外周血T淋巴细胞亚群以及NK细胞和B细胞 ,同时通过检测分泌细胞因子γ干扰素 (IFN γ)、白细胞介素 4(IL 4)的CD+ 4细胞方法 ,测出相应TH1、TH2细胞的百分比 ,并与2 8例正常儿童进行比较。同时对 3 5例支原体肺炎患儿中的 3 0例进行了血清免疫球蛋白及精制结核菌素 (PPD)皮肤试验。全部患儿均系在我院住院的患儿 ,男 15例 ,女 2 0例 ,年龄 3～ 13岁 ,平均 9岁。对照组男 14例 ,女 14例 ,年龄 3～ 12岁 ,平均 7岁。结果　支原体肺炎患儿急性期外周血CD+ 3 、CD+ 4T细胞百分率为 68 0 0± 6 66及 3 7 86± 5 84,较对照组 63 71± 7 92及 3 4 54± 6 2 3高 ,(P <0 0 5) ;患儿外周血TH1细胞百分率为 14 13± 8 46,对照组为 2 0 77± 6 89,两者差异有非常显著意义 (P =0 0 0 1)。NK细胞及TH1/TH2比值在患儿组降低 (P分别为 <0 0 1和 <0 0 5)。两组间CD8、TH2、B细胞百分率及CD4/CD8比值差异无显著意义。 3 0例患儿之血清免疫球蛋白与同龄正常儿童比较 ,IgG全部正常 ;IgA升高 7例 ;IgM升高 4例。皮肤P     

手足口病患儿淋巴细胞亚群和免疫球蛋白及补体C3、C4水平分析

目的 分析淋巴细胞亚群、免疫球蛋白及补体C3、C4在手足口病患儿免疫状态评估中的临床应用价值。方法 选取282例手足口病患儿为手足口病组,130例健康儿童为健康对照组;检测两组外周血CD3⁺、CD4⁺、CD8⁺T淋巴细胞、CD19+B淋巴细胞、CD56+自然杀伤细胞比例,CD4⁺/CD8⁺、IgA、IgM、IgG和补体C3、C4水平。结果 多因素分析显示,手足口病组CD3⁺、CD4⁺、CD8⁺T淋巴细胞比例及补体C3、C4水平低于健康对照组（P < 0.05）,CD56+自然杀伤细胞比例、IgG水平高于健康对照组（P < 0.05）。单独效应分析显示,0岁~手足口病组CD4⁺/CD8⁺高于健康对照组（P < 0.05）;0岁~及3岁~的男性手足口病组IgM水平高于健康对照组（P < 0.05）;3岁~男性及0岁~女性手足口病组IgA水平低于健康对照组（P < 0.05）。结论 手足口病患儿存在细胞免疫及体液免疫功能紊乱,监测淋巴细胞亚群、免疫球蛋白水平可以为手足口病患儿的免疫状态评估提供实验室依据。     

肺炎支原体肺炎T细胞亚群免疫球蛋白水平变化的研究

目的：为了正确认识肺炎支原体肺炎(MPP)患儿免疫状态,该研究检测了MPP患儿外周血T细胞亚群、免疫球蛋白的变化,旨在探讨MPP患儿免疫功能的特点。方法：采用流式细胞仪技术(FCM)检测了32例支原体肺炎患儿外周血T细胞亚群及免疫球蛋白,并与28例正常儿童进行比较。结果：MPP患儿急性期外周血CD3,CD4,CD8,CD4/CD8分别为57.30±6.21个/μL,32.70±6.52个/μL,24.9±2.41个/μL,1.31±0.33,恢复期外周血CD3,CD4,CD8,CD4/CD8分别为58.20±6.10个/μL,34.92±5.93个/μL,25.87±4.72个/μL,1.39±0.42,CD4,CD4/CD8较对照组低,P<0.05。MPP患儿外周血急性期IgG,IgA,IgM分别为9.93±2.67g/L,1.63±0.69g/L,1.73±0.83g/L,恢复期分别为11.45±2.97g/L,1.94±0.84g/L,2.17±1.23g/L,IgG,IgM较对照组高,P<0.01。IgA与对照组比较无明显差异。结论：肺炎支原体肺炎时患儿存在细胞免疫和体液免疫失调,该研究为临床应用免疫调节剂提供了理论依据。     

Antitissue transglutaminase and antithyroid autoantibodies in children with Down syndrome and celiac disease

OBJECTIVES: We measured circulating autoantibodies and evaluated the potential of circulating antitissue transglutaminase (tTG) antibodies to determine the presence of celiac disease (CD) in children with Down syndrome. METHODS: An ELISA based on recombinant human tTG was used to measure the levels of immunoglobulin A and immunoglobulin G antibodies in serum samples from 72 children with Down syndrome, 52 children with biopsy-verified CD, 21 disease controls with a normal small intestinal mucosa and 23 healthy controls. Of the 72 Down syndrome children, 11 under-went a small intestinal biopsy. RESULTS: Four of 72 children with Down syndrome were diagnosed as having CD and three of them had serum levels of immunoglobulin A tTG antibodies greater than 6 U/mL (668, 147 and 7 U/mL). One Down syndrome child with biopsyproven CD had normal levels of immunoglobulin A tTG. Two Down syndrome children had increased levels of immunoglobulin A tTG (13 and 7 U/mL) but none of these children had an intestinal biopsy performed. Of the 52 CD subjects (median 664 U/mL) one was negative for immunoglobulin A tTG (5 U/mL) and all healthy controls (median 1.2 U/mL) and disease controls (median 0.9 U/mL) had immunoglobulin A tTG antibody levels less than 6 U/mL. Two of four Down syndrome children with CD and 36 of 52 celiac children had increased serum levels of immunoglobulin G tTG antibodies. There was no correlation between the serum levels of tTG and antithyroid autoantibodies. CONCLUSIONS: Although the diagnosis of CD depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides a useful complementary diagnostic method for CD in children with Down syndrome.     

X-linked hyper IgM syndrome: a novel sequence variant associated with an atypical mild phenotype

X-linked hyper IgM syndrome is associated with abnormalities in the gene encoding CD40 ligand (CD40LG). A typical phenotype evolves during infancy in affected males. This phenotype includes neutropenia, dysgammaglobulinemia, bacterial sinopulmonary infections, and opportunistic infections. In the absence of the typical phenotypic features, clinicians must maintain a high level of suspicion for X-linked hyper IgM syndrome. We describe a unique hemizygous CD40LG mutation which was discovered in a 12-year-old boy with chronic severe neutropenia, a normal IgG level, and absence of sinopulmonary or opportunistic infections. The clinical implications of this mutation and associated atypical phenotype are discussed.