Yonsei Med J.  2020 Jun;61(6):542-546. 10.3349/ymj.2020.61.6.542.

Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea

  • 1Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 2Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea
  • 3Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
  • 4Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
  • 5Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
  • 6Department of Pediatrics, Inha University Medical Center, Incheon, Korea
  • 7Center for Pediatric Cancer, National Cancer Center, Goyang, Korea
  • 8Department of Pathology, National Cancer Center, Goyang, Korea
  • 9Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
  • 10Department of Pathology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea


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 highdose, 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.


Activated phosphoinositide 3-kinase delta syndrome1; sirolimus; Korea
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