Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia.
Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia.
复制标题
核因子 kappaB 必需调节剂缺陷儿童，患有免疫缺陷但无无汗性外胚层发育不良。
DOI：
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发表时间：
2004
影响因子：
14.2
通讯作者：
V. Wahn
中科院分区：
文献类型：
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作者：
T. Niehues;J. Reichenbach;J. Neubert;S. Gudowius;A. Puel;G. Horneff;E. Lainka;U. Dirksen;H. Schroten;R. Döffinger;J. Casanova;V. Wahn
背景
X 连锁核因子 kappaB 必需调节因子 (NEMO) 基因的无定形突变会导致色素失禁，这对半合子男性患者来说是致命的。男性患者的亚形性 NEMO 突变会导致无汗性外胚层发育不良 (EDA) 并伴有免疫缺陷。
目标
报告一名携带 NEMO 突变且表现出免疫缺陷但无 EDA 的儿童的临床特征。
方法
临床护理记录、图表审查、标准免疫学和微生物实验室技术、NEMO 基因突变分析。
结果
患者自15个月大起，就患有鸟分枝杆菌病，最初为多发性腺炎，随后出现播散性骨髓炎和皮炎。此外，流感嗜血杆菌和肺炎链球菌感染导致支气管扩张。免疫学检查显示，与高 IgM 表型相关的 PBMC 产生的 IFN-γ 较低。尽管使用 4 种药物抗分枝杆菌疗法、连续皮下注射 IFN-γ 、重复抗生素治疗和静脉注射免疫球蛋白替代的重复周期进行治疗，男孩仍然患有慢性病。 12岁时，尽管接受了大剂量阿昔洛韦治疗，但病情仍因严重的自身免疫性溶血性贫血和最终致命的单纯疱疹病毒1型脑炎而并发。尽管他没有表现出任何 EDA 迹象，但发现了一种新型的致病性 NEMO 亚形突变（外显子 2 中的 110-111insC）。
结论
该病例表明，NEMO 突变半合子患者在没有 EDA 的情况下也可能出现免疫缺陷。因此，尽管缺乏 EDA，仍应在选定的免疫缺陷儿童中进行 NEMO 调查。
BACKGROUND
Amorphic mutations in the X-linked nuclear factor kappaB essential modulator ( NEMO ) gene cause Incontinentia pigmenti, which is lethal in hemizygous male patients. Hypomorphic NEMO mutations in male patients lead to anhidrotic ectodermal dysplasia (EDA) with immunodeficiency.
OBJECTIVE
To report the clinical features of a child bearing a NEMO mutation who displayed an immunodeficiency without EDA.
METHODS
Documentation of clinical care, chart review, standard immunologic and microbiological laboratory techniques, mutation analysis of the NEMO gene.
RESULTS
Since the age of 15 months, the patient had Mycobacterium avium disease, beginning with multiple adenitis, later followed by disseminated osteomyelitis and dermatitis. In addition, Haemophilus influenzae and Streptococcus pneumoniae infections led to bronchiectasis. An immunologic work-up revealed a low production of IFN-gamma by PBMCs associated with a hyper-IgM phenotype. Despite treatment using repeated cycles of a 4-drug antimycobacterial regimen, continuous subcutaneous IFN-gamma, repeated antibiotic treatment, and intravenous immunoglobulin substitution, the boy remained chronically ill. At the age of 12 years, the disease was complicated by severe autoimmune hemolytic anemia and eventually fatal herpes simplex virus 1 encephalitis despite high-dose acyclovir therapy. Although he did not present any sign of EDA, a novel type of disease-causing hypomorphic NEMO mutation (110-111insC in exon 2) was identified.
CONCLUSION
This case demonstrates that patients hemizygous for NEMO mutations can present with an immunodeficiency without EDA. An investigation of NEMO should thus be undertaken in selected children with immunodeficiency despite the lack of EDA.