David Dale, MD from the University of Washington and Sarah Cohen, MD, Medical Director, Rare Diseases at X4 Pharmaceuticals discuss the results from the Phase 2 dose-escalation and long-term extension study of mavorixafor in WHIM syndrome.

WHIM syndrome is a rare, congenital primary immunodeficiency disorder associated with severe neutropenia that affects all ages. However, due to the heterogeneous presentation of the disease, coupled with lack of awareness of the condition, the diagnosis may be delayed, sometimes even into adulthood. The acronym “WHIM” stands for (W)arts, (H)ypogammaglobulinemia, (I)nfections, and (M)yelokathexis. Myelokathexis refers to an abnormal retention of white blood cells, in the bone marrow, that causes a reduction of immune fighting white blood cells, and most notably the reduction of neutrophils and lymphocytes. Importantly, the acronym WHIM can be misleading because most patients will NOT present with all the symptoms associated with the four letters of the term (W.H.I. or M.), and therefore the diagnosis of the disease may be delayed, or misdiagnosed and, consequently, underdiagnosed.

WHIM syndrome is caused by mutations of the CXCR4 gene that are inherited as an autosomal dominant trait. The CXCR4 protein is a chemokine receptor that is common to both hematopoietic and nonhematopoietic cells. There is evidence that the CXCR4 receptor is involved with B-lymphocyte trafficking throughout the body. Current theory suggests that the mutations, associated with WHIM syndrome, cause abnormal retention of neutrophils in the bone marrow, preventing them from being released in the blood, resulting in neutropenia, which can present an increased risk for recurrent or severe infections for patients

For more information on WHIM syndrome, visit the WHIM Syndrome Learning Center.