Sex: F
Vaccine: RUB
Symptoms: Lymphopenia, Measles, Monocytopenia, Neutropenia, Vaccination failure
Clinical narrative: Phenotypic characterization of a family with WHIM syndrome. A family was referred to the Institute for evaluation of possible WHIM syndrome. Patients P1 and P2 are 9-year-old male and 5-year-old female siblings; patient P3 was the 34-year-old mother of P1 and P2; and patient P4 is the 53-year-old grandmother of P1 and P2. Clinical features are summarized. Blood for genetic testing was also obtained from a sibling brother and the father of P1 and P2, both of whom lacked a history consistent with congenital immunodeficiency. This report was about P3, a 34 years old female patient. The patient's medical history included abnormal pap smears, HPV infection and abnormal pap smears. The patient was vaccinated with rubella. P3 had measles as a child despite vaccination with the rubella and failure of vaccination. P1 had multiple clusters of warts on his hands near the finger tips and several warts on his face since age 3 that did not respond to topical salicylic acid or 5-nuorouracil. P2 did not have warts. P3 had abnormal Pap smears in 2000 and 2009 that were consistent with HPV infection. Although P1, P2 and P3 all had serum lg levels above the lower limit of the normal range and a protective titer after diphtheria and tetanus vaccination, they also had a history of clinical failure of vaccination. In particular, P1 and P2 had virologically documented influenza twice despite receiving the annual seasonal vaccination more than 1 month before disease onset, and P3 had measles as a child despite vaccination with the rubella vaccine. All 3 patients had frequent bacterial infections involving the respiratory tract, including pharyngitis, sinusitis, pneumonia, and otitis. The latter eventually led to bilateral sensorineural hearing loss and speech problems in P1 and P2 with a need for hearing aids in P1. P2 also had recurrent vaginal yeast infections after treatment with antibiotics. Congenital neutropenia was diagnosed in P1 and P2 and their absolute neutrophil counts (ANCs) were noted to range from 0.4-1.3* 10^9/L and to increase during infections. The mother, P3, had a history of mild neutropenia (twice documented recently as 1.4 and 1.95 x 10^9/L at the institute). The grandmother, P4, had a history of neutropenia (1.4 x 10^9/L at the institute) and a hysterectomy at age 20 for a diagnosis of unspecified malignancy, but did not have a history of recurrent infections, vaccine failure, or persistent warts. P1, P2, and P3 all had monocytopenia documented on multiple occasions, and P3 was consistently lymphocytopenic. At the institute, the absolute monocyte count for P4 was at the lower limit of normal. At age 3, a BM biopsy performed on P1 showed myelokathexis (increased numbers of mature neutrophils in BM associated with neutropenia) with an eyeglass-shaped neutrophil in which the nuclear lobes were connected by a long filament. Chromosomal analysis revealed a normal male karyotype with no observed clonal abnormalities. BM evaluation had not been performed of P2, P3, or P4. Because of recurrent infections despite vaccination and a daily prophylactic antibiotic, P2 was treated with G-CSF (Neupogen; Amgen) with an excellent response, including marked reduction in the incidence of infections. The available clinical history and laboratory values presented by this family suggested the possibility of WHIM syndrome. Nevertheless, as with other WHIM patients, vaccination failed to protect CXCR4 (E343K) patients P1 and P2 from influenza and P3 from a measles infection, suggesting that their B-cell function might be at least partially impaired. This is one of several reports from the same literature. Additional information has been requested.