Gain of function mutations in the p110δ catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) classified as activated phosphoinositide 3-kinase delta syndrome (APDS) are the cause of a primary immunodeficiency characterized by recurrent sinopulmonary infections, and lymphoproliferation. Previously, autoimmunity and Epstein-Barr virus–related B-cell lymphoma have been documented for patients with APDS; here, we present a case that extends the picture, as the patient shows the full diagnostic criteria of hemophagocytic lymphohistiocytosis at 6 months of age. He experienced Hodgkin lymphoma as a 2.5-year-old baby. Next-generation sequencing returned a de novo heterozygous missense variant in PIK3CD (LRG_191t1: c.3061G>A; p.Glu1021Lys), confirming the primary immunodeficiency. After 2 courses of ifosfamide, cisplatin, and etoposide combined with brentuximab, the patient successfully underwent allogeneic hematopoietic stem cell transplantation from his HLA full matched sister, and he has been well for 18 months after that. The hematologist treating Hodgkin lymphoma and/or hemophagocytic lymphohistiocytosis should be vigilant about the possible underlying immune deficiency, and they should consider APDS in their differential diagnosis.
*Department of Pediatrics, Division of Pediatric Immunology
§Department of Pediatrics, Division of Pediatric Hematology Oncology & Pediatric HSCT Unit
∥Department of Pathology
¶Department of Nuclear Medicine, Faculty of Medicine, Erciyes University
#Molecular Biology and Genetic Department, Gevher Nesibe Genom and Stem Cell Institution, Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
†Department of Pediatrics, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
‡Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
M.C., A.O., M.K., T.P., E.U.: medical practices. N.Z., S.C.C.C., M.R., I.S., O.C., U.A., Y.B., C.K.: laboratory & genetic practices. M.C., N.Z., S.C.C.C., A.O., E.Y., E.U.: concept. N.Z., M.C., S.C.C.C., A.O., M.R., I.S., Y.B., C.K., E.U.: analysis or interpretation. M.C., N.Z., S.C.C.C, A.O., M.R., E.U.: literature search. M.C., N.Z., S.C.C.C., A.O., M.K., M.R., I.S., Y.B., C.K., E.U.: writing.
The authors declare no conflict of interest.
Reprints: Ekrem Unal, MD, Department of Pediatrics, Division of Pediatric Hematology & Oncology, Erciyes University Medical Faculty, Melikgazi, Kayseri 38039, Turkey (e-mails: email@example.com; firstname.lastname@example.org).
Received June 13, 2018
Accepted February 21, 2019