Immunologic Disorders

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome

Key Clinical and Laboratory Features

Common clinical features: Chronic neutropenia that may cause susceptibility to recurrent, severe bacterial infections and sepsis. Recurrent bacterial sinopulmonary infections (otitis media, sinusitis, bronchitis, pneumonias) caused by hypogammaglobulinemia. Severe warts/papillomas (cutaneous/vaginal)
Other clinical features: Viral-associated (HPV, EBV) neoplasias
Physical exam: Cutaneous or vaginal warts and papillomas.
Common laboratory features: Neutropenia, B-cell lymphopenia, lack of switched-memory B cells, hypogammaglobulinemia, decreased specific antibody responses, bone marrow biopsy shows myelokathesxis

	TEST	COMMENTS
GENE	CXCR4 Gene Sequencing	The gold standard for confirming a diagnosis of WHIM syndrome in a patient with suggestive symptoms.
PROTEIN AND FUNCTION	N/A	There are currently no available clinical tests to evaluate CXCR4 protein expression or function although neutropenia is a surrogate measure because neutrophils are not able to traffic out of the bone marrow normally in the absence of functional CXCR4.
OTHER		Complete blood count with differential: Neutropenia is consistently present. Lymphocyte subset analysis: B-cell lymphopenia is common. Quantitative immunoglobulin levels: IgG is typically low. Specific antibody titers: Typically low. Bone marrow biopsy: Myelokathexis is typical.