David Dale, MD at the University of Washington Medical Center in Seattle, discusses some of the challenges in diagnosing WHIM syndrome.

Individuals with WHIM syndrome have severe congenital neutropenia. In addition, because they also have profound white blood cell (WBS) deficiencies characterized as panleukopenia, WHIM syndrome is also classified as a severe combined immunodeficiency. B lymphopenia is particularly severe, and this probably accounts in part for hypogammaglobulinemia. Some patients also have developmental defects of the cardiovascular, urogenital, and nervous systems, although only the cardiovascular defects appear to be clinically significant.

The first symptoms that appear in very young patients are recurrent bacterial infections (especially respiratory infections like sinusitis, otitis media, and pneumonia) and cellulitis. Another challenge to diagnosis is the transient normalization of white blood cells during acute infections, which is the moment when patients most commonly seek medical attention. This can lead clinicians into missing the key sign of low neutrophils. As a result, diagnosis is often delayed until other characteristics of WHIM appear, and delayed diagnosis challenges the initiation of appropriate treatment.

While identification of the most notable signs of WHIM syndrome is straightforward; diagnosis is challenging because of its rarity. A detailed patient history often reveals recurrent infections in the patient. Two thirds of patients have a family history of WHIM syndrome. Complete blood count testing (with differential) will yield abnormally low neutrophil counts (unless bolstered during episodes of infection), low total white blood cells and low lymphocytes, and about have the patients have mildly low IgG, IgM or IgA concentrations. More than half of the patients will report a history of treatment refractory warts. Warts may be extensive and involve the ano-genital area. If WHIM syndrome is suspected, the diagnosis can be confirmed through genetic tests to identify mutations in the CXCR4 gene. If performed, bone marrow biopsy will reveal myelokathexis.