Abstract：
Chronic granulomatous disease (CGD) primarily results from inherited defects in components of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex. These include gene defects in cytochrome B-245/558 subunit α/β and neutrophil cytosolic factors 1, 2, and 4. Recently, homozygous loss-of-function variants in cytochrome B-245 chaperone 1 gene (CYBC1) have been discovered to cause CGD (CYBC1-CGD). Data on variant-proven CGD from low-income countries, the most underprivileged regions of the world, remain sparse due to numerous constraints. Herein, we report the first cohort of patients with CGD from Nepal, a low-income country in the Himalayas\' challenging terrain. Our report includes a description of a new case of CYBC1 deficiency who was first diagnosed with CGD at our center. Only a dozen cases of CYBC1-CGD have been described in the literature thus far which have been reviewed comprehensively herein. Most of these patients have had significant infections and autoimmune/inflammatory manifestations. Pulmonary and invasive/disseminated bacterial/fungal infections were the most common followed by skin and soft-tissue infections. Inflammatory bowel disease (IBD) was the most common inflammatory manifestation (median age at diagnosis: 9 years) followed by episodes of recurrent/prolonged fever. Other autoimmune/inflammatory manifestations reported in CYBC1-CGD include acute pancreatitis, hemophagocytic lymphohistiocytosis, systemic granulomatosis, interstitial lung disease, arthritis, autoimmune hemolytic anemia, uveitis, nephritis, and eczema. Our analysis shows that patients with CYBC1-CGD are at a significantly higher risk of IBD-like illness as compared to other forms of CGD which merits further confirmatory studies in the future.
摘要：
慢性肉芽肿病（CGD）主要是由烟酰胺腺嘌呤二核苷酸磷酸氧化酶酶复合物成分的遗传缺陷引起的。这些包括细胞色素B-245/558亚基α/β和嗜中性粒细胞胞质因子1、2和4中的基因缺陷。最近,已发现细胞色素B-245伴侣1基因（CYBC1）中的纯合功能丧失变体引起CGD（CYBC1-CGD）。来自低收入国家的经变异证明的CGD数据，世界上最贫困的地区，由于许多限制，保持稀疏。在这里，我们报告了第一批来自尼泊尔的CGD患者，喜马拉雅山的一个低收入国家充满挑战的地形。我们的报告包括对我们中心首次诊断为CGD的CYBC1缺乏症的新病例的描述。迄今为止,文献中仅描述了十几种CYBC1-CGD病例,本文对其进行了全面综述。这些患者中的大多数具有显著的感染和自身免疫/炎症表现。肺部和侵袭性/播散性细菌/真菌感染最常见，其次是皮肤和软组织感染。炎症性肠病（IBD）是最常见的炎症表现（诊断时的中位年龄：9岁），其次是反复/长期发烧。CYBC1-CGD报告的其他自身免疫/炎症表现包括急性胰腺炎，噬血细胞淋巴组织细胞增生症，全身性肉芽肿病,间质性肺病,关节炎,自身免疫性溶血性贫血,葡萄膜炎,肾炎,还有湿疹.我们的分析表明，与其他形式的CGD相比，CYBC1-CGD患者患IBD样疾病的风险明显更高，值得将来进行进一步的确证研究。
