WHIM syndrome is a rare primary immunodeficiency that is characterized by neutropenia with myelokathexis, hypogammaglobulinema, susceptibility to human papilloma virus infection. It is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4).
We report a group of 7 patients (6 from unrelated families, one family - P3 is a son of P4) 1-40 years (M – 4y) with CXCR4 mutations. The mutations were detected via NGS targeted panel sequencing and/or Sanger’s sequencing.
All patients manifested with neutropenia, myelokathexis and lymphopenia was observed at the onset of the disease. Four of them had the same mutation (p.R334X). Hypogammaglobulinemia was observed in 6 patients where as P2 showed borderline levels. Severe infections (pneumonia and lung abscess) were observed in 2 patients. Skin warts were observed only in adult patient (P4). 4 patients had variable congenital heart defects, three patients had renal abnormalities. 6 patients were treated with prophylactic antimicrobials, IVIG and subcutaneous injections of G-SCF (3 - 10 μg/kg/d). 2 patients underwent HSCT from a 10/10 (P6) and 9/10 (P3) matched unrelated donor, they are currently 5 years and 60 days post-transplant, respectively, with full donor chimerism.
CXCR4 defects need to be considered in patients with chronic neutropenia and congenital anomalies, especially heart and renal defects, despite lack of severe infections and warts. Based on our experience WHIM can be effectively treated with HSCT, though longer follow-up is needed.