Background Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-of-function mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type of causative mutation, APDS is classified into two types: APDS 1 and APDS 2. To date, less than 100 cases of APDS have been reported. Clinical symptoms of APDS result from impaired immune regulation and are clinically manifested by recurrent infections, allergies, lymphoproliferation and autoimmunity. They show similarity to other PIDs. Therefore, many patients were diagnosed incorrectly. The availability of genetic testing has allowed establishing the correct diagnosis in increasing number of patients suffering from APDS. Case presentations The first male patient presented in infancy with recurrent infections. Subsequently he was found to suffer from hepatosplenomegaly, early portal hypertension, massive lymphoproliferation and hypogammaglobulinemia. The common E1021K mutation in the PI3KCD gene was identified. The patient underwent successful hematopoietic stem cell transplantation with resolution of most symptoms. The second patient suffered from persistent growth retardation since early life, facial dysmorphism and recurrent respiratory infections from early childhood. He was found to have systemic lympho-proliferation, panhypoglobulinemia and impaired antibody responses to vaccines. The introduction of NGS in Poland enabled rapid identification of a mutation in the PI3KR1 gene. Growth hormone administration seemed to have worsened the lymphoproliferation. Conclusions Patients with suspected common variable immunodeficiency (CVID) and additional symptoms, such as allergy, facial dysmorphia, short stature, enhanced lymphoproliferation and lack of adequate response to human immunoglobulin replacement therapy, should be considered for NGS-based genetic testing. It may substantially shorten the time needed to establish the correct diagnosis, direct appropriate treatment and avoid potentially harmful therapies. To date, few cases of APDS have been described. It is important to report each of them to establish clinical indices and laboratory biomarkers of APDS 1 and APDS 2, to develop the standards of care in these conditions.

中文翻译：

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活化的磷酸肌醇 3-激酶 δ 综合征 1 和 2（APDS 1 和 APDS 2）：基于两个男孩的临床表现的异同。

背景 活化的 PI3K δ 综合征 (APDS) 属于原发性免疫缺陷疾病 (PID) 的异质组。新一代测序 (NGS) 的进展使得能够识别磷酸肌醇 3-激酶 (PI3K) 基因中的功能获得性突变。根据致病突变的类型，APDS 分为两种类型：APDS 1 和 APDS 2。迄今为止，报告的 APDS 病例不到 100 例。APDS的临床症状由免疫调节受损引起，临床表现为反复感染、过敏、淋巴组织增生和自身免疫。它们显示出与其他 PID 的相似性。因此，很多患者被误诊。基因检测的可用性允许在越来越多的患有 APDS 的患者中建立正确的诊断。病例介绍 第一位男性患者在婴儿期出现反复感染。随后，他被发现患有肝脾肿大、早期门静脉高压症、大量淋巴组织增生和低丙种球蛋白血症。鉴定了 PI3KCD 基因中常见的 E1021K 突变。患者接受了成功的造血干细胞移植，大部分症状得到缓解。第二名患者从小就患有持续性生长迟缓、面部畸形和儿童早期反复呼吸道感染。他被发现有全身性淋巴增殖、全低球蛋白血症和对疫苗的抗体反应受损。在波兰引入 NGS 可以快速识别 PI3KR1 基因的突变。生长激素给药似乎恶化了淋巴增殖。结论 疑似常见变异性免疫缺陷 (CVID) 和其他症状的患者，如过敏、面部畸形、身材矮小、淋巴增殖增强和对人免疫球蛋白替代疗法缺乏足够反应，应考虑进行基于 NGS 的基因检测。它可以大大缩短建立正确诊断、指导适当治疗和避免潜在有害疗法所需的时间。迄今为止，很少有 APDS 病例被描述。重要的是报告它们中的每一个，以建立 APDS 1 和 APDS 2 的临床指标和实验室生物标志物，以制定这些条件下的护理标准。对于基于 NGS 的基因检测，应考虑淋巴细胞增殖增强和对人免疫球蛋白替代疗法缺乏足够反应。它可以大大缩短建立正确诊断、指导适当治疗和避免潜在有害疗法所需的时间。迄今为止，很少有 APDS 病例被描述。重要的是报告它们中的每一个，以建立 APDS 1 和 APDS 2 的临床指标和实验室生物标志物，以制定这些条件下的护理标准。对于基于 NGS 的基因检测，应考虑淋巴细胞增殖增强和对人免疫球蛋白替代疗法缺乏足够反应。它可以大大缩短建立正确诊断、指导适当治疗和避免潜在有害疗法所需的时间。迄今为止，很少有 APDS 病例被描述。重要的是报告它们中的每一个，以建立 APDS 1 和 APDS 2 的临床指标和实验室生物标志物，以制定这些条件下的护理标准。