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WHIM Syndrome (Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis syndrome) is a rare congenital immunodeficiency disorder.
It is characterized by chronic noncyclic neutropenia.
It has an autosomal dominant pattern of inheritance.
WHIM syndrome results from mutations in the gene for the chemokine receptor, CXCR4
A molecular disease arising from gain-of-function mutations in CXCR4.
CXCR4 mutations result in a carboxy-terminus truncation of the receptor of between ten and 19 residues.
The gene mutant is located on chromosome 2q21.
The truncation of the receptor protein results in the inability of downregulation after stimulation, so that the receptor remain in an activated state.
It is primarily caused by an aberrant chemokine.
Patients have an increased susceptibility to bacterial and viral infections.
Patients are prone to human papilloma virus, resulting in warts on the hands and feet starting in childhood.
Myelokathexis refers to retention of neutrophils in the bone marrow.
Lymphocytes and IgG antibody levels are often low.
WHIM like mutations in CXCR4 were recently identified in patients with Waldenström’s macroglobulinemia, a B-cell malignancy.
The presence of CXCR4 WHIM mutations has been associated with clinical resistance to ibrutinib in patients with Waldenström’s macroglobulinemia.
Management:
Infusions of immune globulin can reduce the frequency of bacterial infections.
G-CSF or GM-CSF therapy improves blood neutrophil counts.
Plerixafor, is a specific CXCR4 antagonist, as a potential mechanism-based therapy for the disease.
Plerixafor may increase in white blood cell count and may also prove to have anti-human papillomavirus (HPV) properties.