López Méndez Angélica, Arias Villaverde Airam A, Sánchez López Abraham P, Gloria Méndez Elizabeth, Hernández Zamora María R, Ramírez Lobato Alesha, Aguirre Quintero María F, Mondragón Rosas Emilio, González Flores José Emiliano
Pediatric Nephrology, Instituto Nacional de Pediatría (INP), Mexico City, MEX.
School of Medicine and Health Sciences, Tecnológico de Monterrey Mexico City Campus, Mexico City, MEX.
Cureus. 2025 Aug 12;17(8):e89884. doi: 10.7759/cureus.89884. eCollection 2025 Aug.
Activated PI3K delta syndrome (APDS) is a rare primary immunodeficiency caused by gain-of-function (GOF) mutations in or , leading to immune dysregulation. It typically presents with recurrent respiratory infections, lymphoproliferation, autoimmunity, and increased risk of malignancy. Although gastrointestinal involvement has been described, it is less frequent and often underrecognized. To our knowledge, this is the first genetically confirmed case of APDS in Mexico, highlighting an atypical presentation with significant gastrointestinal symptoms. This case underscores the challenges in diagnosing APDS in settings with limited access to genetic testing and emphasizes the importance of early recognition in patients with complex infectious and inflammatory histories. A four-year-old male presented with chronic diarrhea, failure to thrive, and recurrent respiratory infections since infancy. Clinical evaluation revealed hepatosplenomegaly, generalized lymphadenopathy, severe malnutrition, and infections with , and parainfluenza virus. Endoscopic findings included malakoplakia and gastritis. A multigene panel identified a heterozygous pathogenic variant in (c.3061G>A, p.Glu1021Lys), confirming APDS1. Additionally, a risk variant in was detected, which may have contributed to the gastrointestinal phenotype. The patient was managed with immunoglobulin replacement, antimicrobial prophylaxis, and multidisciplinary care, leading to clinical improvement. This case illustrates the variable presentation of APDS and highlights the importance of including primary immunodeficiencies in the differential diagnosis of children with recurrent infections and gastrointestinal manifestations. Early genetic confirmation facilitates tailored management and improves outcomes. Future research should explore genotype-phenotype correlations, especially in patients with multiple genetic variants, and assess the long-term benefits of targeted therapies such as PI3Kδ inhibitors.
活化磷脂酰肌醇-3-激酶δ综合征（APDS）是一种罕见的原发性免疫缺陷病，由PIK3CD或PIK3R1基因的功能获得性（GOF）突变引起，导致免疫失调。其典型表现为反复呼吸道感染、淋巴增殖、自身免疫以及恶性肿瘤风险增加。虽然已有胃肠道受累的描述，但较为少见且常未被充分认识。据我们所知，这是墨西哥首例经基因确诊的APDS病例，突出了伴有明显胃肠道症状的非典型表现。该病例强调了在基因检测条件有限的情况下诊断APDS的挑战，并强调了对具有复杂感染和炎症病史患者进行早期识别的重要性。一名4岁男性自婴儿期起就出现慢性腹泻、生长发育迟缓及反复呼吸道感染。临床评估发现肝脾肿大、全身淋巴结肿大、严重营养不良以及感染了白色念珠菌、隐孢子虫和副流感病毒。内镜检查结果包括软斑病和淋巴细胞性胃炎。一个多基因检测面板在PIK3CD基因中鉴定出一个杂合致病性变异（c.3061G>A，p.Glu1021Lys），确诊为APDS1。此外，还检测到PIK3R1基因中的一个风险变异，这可能导致了胃肠道表型。该患者接受了免疫球蛋白替代治疗、抗菌预防和多学科护理，临床症状有所改善。本病例说明了APDS的表现具有多样性，并强调了在反复感染和有胃肠道表现的儿童鉴别诊断中纳入原发性免疫缺陷病的重要性。早期基因确诊有助于进行针对性治疗并改善预后。未来的研究应探索基因型与表型的相关性，特别是在具有多个基因变异的患者中，并评估PI3Kδ抑制剂等靶向治疗的长期益处。
