Here, we reported a classical APDS case with PIK3CDE1021K gene mutation with recurrent respiratory tract infections, Cryptosporidium enteritis, high serum level of IgM, anemia, lymphoproliferation, and inverted CD4+/CD8+ ratio, successfully treated with haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from her brother. Here, CD40LG is linked to Respiratory tract infection.