Activated
phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of
phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of
sirolimus, a
mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received
sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid
hyperplasia in the gastrointestinal tract. The median trough level of
sirolimus was 5.5 ng/mL (range, 2.8-7.5) at a dose of 2.6-3.6 mg/m². Two patients who needed high-dose, short-interval,
immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating
sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The
IgG trough level after
sirolimus treatment (median, 594 mg/dL; range, 332-799 mg/dL) was significantly higher than that before
sirolimus treatment (median, 290 mg/dL; range, 163-346 mg/dL) (p<0.001). One episode of elevated serum
creatinine with a surge of
sirolimus (Patient 2) and episodes of
neutropenia and oral
stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose
sirolimus may alleviate clinical manifestations thereof, including
hypogammaglobulinemia.