TY - JOUR
T1 - Case Report
T2 - Clinical manifestations of uncommon monogenic disorders: revisiting activated phosphoinositide 3-kinase delta syndrome 2
AU - Shamriz, Oded
AU - Mandola, Amarilla
AU - Simon, Amos J.
AU - Lev, Atar
AU - Attal, Pierre
AU - Nadler, Chen
AU - Barel, Ortal
AU - Khavkin, Yulia
AU - Eisenberg, Rachel
AU - Somech, Raz
AU - Toker, Ori
N1 - Publisher Copyright:
2025 Shamriz, Mandola, Simon, Lev, Attal, Nadler, Barel, Khavkin, Eisenberg, Somech and Toker.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Aim: Pediatricians are trained to identify recurrent or unusual infections in children, prompting evaluation for inborn errors of immunity (IEI). Some monogenic IEI, however, may present atypically. This study describes our experience with children diagnosed with activated phosphoinositide 3-kinase delta syndrome (APDS2) including unusual presentations. Methods: A retrospective review was conducted on two children diagnosed with APDS2 at Shaare Zedek and Sheba Tel-Hashomer Medical Centers in Israel. Both patients underwent immune assessments, genetic testing, and treatment between 2019 and 2024. Results: Two patients, a 17-year-old female (P1) and a 7-year-old male (P2), were diagnosed with APDS2 after presenting with recurrent juvenile parotitis (P1) and severe lymphadenopathy (P2). Immunologic evaluation revealed hypogammaglobulinemia and combined immune deficiency. Genetic testing identified PIK3R1 variants (c.1425 + 1G > T in P1 and c.1425 + 1G > C in P2). Both received intravenous immunoglobulins and prophylactic antibiotics. P2 was treated with rapamycin, leading to resolution of lymphadenopathy. Conclusion: This report highlights the clinical presentation of APDS2, a rare monogenic IEI in children, including the atypical manifestation of RJP and the common feature of lymphadenopathy. Pediatricians should stay vigilant for red flags of IEI during clinical evaluations, as early diagnosis and multidisciplinary care are crucial for effective management.
AB - Aim: Pediatricians are trained to identify recurrent or unusual infections in children, prompting evaluation for inborn errors of immunity (IEI). Some monogenic IEI, however, may present atypically. This study describes our experience with children diagnosed with activated phosphoinositide 3-kinase delta syndrome (APDS2) including unusual presentations. Methods: A retrospective review was conducted on two children diagnosed with APDS2 at Shaare Zedek and Sheba Tel-Hashomer Medical Centers in Israel. Both patients underwent immune assessments, genetic testing, and treatment between 2019 and 2024. Results: Two patients, a 17-year-old female (P1) and a 7-year-old male (P2), were diagnosed with APDS2 after presenting with recurrent juvenile parotitis (P1) and severe lymphadenopathy (P2). Immunologic evaluation revealed hypogammaglobulinemia and combined immune deficiency. Genetic testing identified PIK3R1 variants (c.1425 + 1G > T in P1 and c.1425 + 1G > C in P2). Both received intravenous immunoglobulins and prophylactic antibiotics. P2 was treated with rapamycin, leading to resolution of lymphadenopathy. Conclusion: This report highlights the clinical presentation of APDS2, a rare monogenic IEI in children, including the atypical manifestation of RJP and the common feature of lymphadenopathy. Pediatricians should stay vigilant for red flags of IEI during clinical evaluations, as early diagnosis and multidisciplinary care are crucial for effective management.
KW - APDS2
KW - PIK3R1
KW - combined immune deficiencies
KW - inborn errors of immunity
KW - primary immune deficiencies (PID)
UR - https://www.scopus.com/pages/publications/105004829857
U2 - 10.3389/fped.2025.1570600
DO - 10.3389/fped.2025.1570600
M3 - Article
C2 - 40364814
AN - SCOPUS:105004829857
SN - 2296-2360
VL - 13
JO - Frontiers in Pediatrics
JF - Frontiers in Pediatrics
M1 - 1570600
ER -