Chronic Granulomatous Disease Caused by a Deficiency in p47phox Mimicking Crohn's Disease
Chronic Granulomatous Disease Caused by a Deficiency in p47phox Mimicking Crohn's Disease
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DOI：
10.1016/s1542-3565(04)00292-7
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发表时间：
2004-08-01
影响因子：
12.6
通讯作者：
Bastian, John
中科院分区：
文献类型：
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作者：
Huang, Jeannie S.;Noack, Deborah;Bastian, John
我们描述了2例常染色体隐性慢性肉芽肿病（CGD）在2姐妹中表现出与炎症性肠病一致的图像。该病例为一名10岁女童，有难治性克罗恩结肠炎病史，曾接受积极免疫抑制治疗，随后并发中枢神经系统曲霉病。进一步的评估显示了CGD的诊断，这是一种潜在的免疫缺陷，由于烟酰胺-腺嘌呤磷酸二核苷酸（NADPH）氧化酶的还原形式的遗传缺陷，吞噬细胞不能产生杀微生物的活性氧中间体。在我们的女性患者中，典型的x连锁遗传疾病的诊断表明，她患有三种不常见的常染色体隐性形式的疾病中的一种。研究证实，在她的中性粒细胞中没有NADPH氧化酶的p47（phox）亚基，并且在编码p47（phox）的中性粒细胞胞浆因子1基因中存在纯合二核苷酸缺失。对患者直系亲属的进一步分析显示，2名兄弟姐妹也有相同的纯合突变，其中1人也出现了与克罗恩病诊断一致的慢性结肠炎。这2例病例强调了在推定为炎症性肠病和机会性感染的情况下，对免疫缺陷进行替代诊断的高度临床怀疑的重要性。
We describe 2 cases of autosomal recessive chronic granulomatous disease (CGD) in 2 sisters presenting with a picture consistent with inflammatory bowel disease. The index case is a 10-year-old girl with a history of refractory Crohn's colitis treated with aggressive immunosuppressive therapy whose course subsequently was complicated by central nervous system aspergillosis. Additional evaluation showed a diagnosis of CGD, an underlying immunodeficiency in which phagocytes fail to produce microbicidal reactive oxygen intermediates because of inherited defects in the reduced form of nicotinamide-adenine phosphate dinucleotide (NADPH) oxidase. The diagnosis of a typically X-linked inherited disease in our female patient suggested that she had 1 of the 3 less common autosomal recessive forms of the disease. This was confirmed by studies showing the absence of the p47(phox) subunit of NADPH oxidase in her neutrophils and the presence of a homozygous dinucleotide deletion in the neutrophil cytosolic factor 1 gene that encodes p47(phox). Additional analyses of members of the patient's immediate family showed the same homozygous mutation in 2 siblings, 1 of whom also developed chronic colitis consistent with a diagnosis of Crohn's disease. These 2 cases emphasize the importance of high clinical suspicion for an alternative diagnosis of immune deficiency in the setting of presumed inflammatory bowel disease and opportunistic infection.