Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease primarily presents with recurrent infections, and patients may also present with inflammatory conditions, including noninfectious colitis, and an increased frequency of autoimmunity. We report here a patient with CGD in whom the presentation, unlike the classical presentation of CGD, was predominantly of an inflammatory and autoimmune phenotype. Case presentation A 3-year-old Pakistani female presented with bloody diarrhea since the age of 7 days, followed by the development of perianal abscesses and fistula. There was no other history of recurrent infections. The patient subsequently developed joint pain and stiffness with persistently elevated inflammatory markers and elevated anti-cyclic citrullinate peptide (anti-CCP) antibody titer. She was diagnosed with oligoarticular juvenile idiopathic arthritis and colitis. The diagnosis of CGD was later made and was based on the absence of NADPH oxidase activity in the patient's neutrophils upon phorbol myristate acetate (PMA) stimulation using the dihydrorhodamine-1,2,3 (DHR) flow cytometry test. Targeted next-generation sequencing revealed an unreported deletion mutation in exon 10 as a homozygous loss-of-function variant of the human neutrophil oxidase factor 2 (NCF2) (NCF2: NM_001190789, nucleotide change: c.855_856del:p.T285fs). The gene encodes a protein subunit, p67phox, in the NADPH enzyme complex. Conclusions The case emphasizes the importance of maintaining high clinical suspicion of immunodeficiency and CGD in patients with very-early-onset colitis and autoimmune disorders. This case is important due to its rarity and because it might represent a previously undiscovered mutation, which is possibly more common in the patient's ethnic group. Other mutations in NCF2 have been linked to inflammatory bowel disease and autoimmunity, but without CGD, suggesting similarities in the pathogenesis.

中文翻译：

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NCF2 的一种新突变导致慢性肉芽肿病患者发生极早发性结肠炎和幼年特发性关节炎。

背景慢性肉芽肿病 (CGD) 是一种罕见的原发性免疫缺陷疾病，由烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶复合物缺陷引起。该疾病主要表现为反复感染，患者也可能出现炎症性疾病，包括非感染性结肠炎和自身免疫频率增加。我们在此报告一名 CGD 患者，其表现与 CGD 的经典表现不同，主要是炎症和自身免疫表型。病例介绍 一名 3 岁的巴基斯坦女性，从 7 天开始出现血性腹泻，随后出现肛周脓肿和瘘管。无其他反复感染病史。患者随后出现关节疼痛和僵硬，炎症标志物持续升高，抗环瓜氨酸肽（抗 CCP）抗体滴度升高。她被诊断出患有少关节幼年特发性关节炎和结肠炎。后来做出了 CGD 的诊断，其依据是使用二氢罗丹明-1,2,3 (DHR) 流式细胞术测试，在醋酸佛波醇肉豆蔻酸酯 (PMA) 刺激下，患者的中性粒细胞中没有 NADPH 氧化酶活性。靶向二代测序揭示了外显子 10 中未报告的缺失突变，作为人中性粒细胞氧化酶因子 2 (NCF2) 的纯合功能缺失变体（NCF2：NM_001190789，核苷酸变化：c.855_856del:p.T285fs）。该基因编码NADPH酶复合物中的蛋白质亚基p67phox。结论 该病例强调了对极早发性结肠炎和自身免疫性疾病患者保持高度临床怀疑免疫缺陷和 CGD 的重要性。这个病例很重要，因为它很罕见，而且它可能代表了一种以前未被发现的突变，这种突变在患者的种族中可能更常见。NCF2 的其他突变与炎症性肠病和自身免疫有关，但没有 CGD，这表明发病机制有相似之处。