Purpose

Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients.

Methods

Details of 34 patients’ personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing.

Results

Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture’s results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life.

Conclusion

This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.

中文翻译：

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埃及儿童白细胞粘附缺陷I型临床、免疫学和分子特征分析

目的

白细胞粘附缺陷（LAD）代表一组罕见的遗传性先天性免疫错误（IEI），其特征是细菌感染、脐带残端分离延迟和自身免疫。这项单中心研究旨在描述 34 名 LAD-I 埃及儿科患者的临床、免疫学和分子特征。

方法

记录了 34 名患者的个人病史、临床和实验室检查结果的详细信息；研究人员对 28 名患者的遗传物质进行了研究。通过桑格测序进行突变分析。

结果

最常见的症状是脐炎、皮肤和软组织感染并伴有溃疡愈合不良、脐残端延迟脱落、肺炎反复发作或未消退，其次是慢性中耳炎、肠病、牙周炎；以及反复发作的鹅口疮。所有患者均报告有持续性白细胞增多和中性粒细胞增多，以及 CD18 和 CD11b 缺乏。约 90% 的患者 CD18 表达< 2%。在 28 名接受ITGß2基因测序的患者中检测到 16 种不同的病理基因变异，其中 10 种是新的，6 种是先前报道的。三个家庭接受了产前诊断。患者根据培养结果尽可能使用抗菌药物，并预防性使用甲氧苄啶-磺胺甲恶唑 5 mg/kg，每日一次，并定期进行临床随访。为 4 名患者提供造血干细胞移植（HSCT）。然而，由于疾病的严重性和诊断的延误，58%的患者在生命的最初两年内去世。

结论

这项研究强调了早期诊断和埃及儿童ITGß2基因突变分布的重要性。然而，为了更好地表征该地区的疾病特征，进一步的分子研究仍然是一个具有挑战性的必要性。