Bridging diagnosis of a rare hematological disorder through genetic testing in a young girl with persistent panleukopenia
A 9-year-old girl was referred for evaluation of fever for 2 months without any systemic complaints. She was first born to a non-consanguineously married couple with no significant family history. She had past history of 3 episodes of pneumonia requiring intravenous antimicrobials and hospital admissions. She was noted to have panleukopenia in her blood counts and underwent bone marrow examination twice (reported as normal). However, in view of recurrent infections and chronic persistent leukopenia, she was referred to our center. Systemic examination was unremarkable. Laboratory investigations showed persistently low total white cell counts (TLC) (table 1). Repeat bone marrow aspiration showed hypercellular marrow with no atypical cells. With a suspicion of underlying inborn error of immunity (IEI), genetic analysis was done which showed a heterozygous novel mutation in exon 1 of CXCR4 (c.1012C>T, p. Arg338Ter). A fresh and detailed re-look at the bone marrow aspirate revealed evidence of myelokathexis (Fig. 1). A diagnosis of Warts, Hypogammaglobulinemia, Infections and Myelokathexis syndrome (WHIMS) was made and she was treated with 1 μg /kg/day of subcutaneous granulocyte colony-stimulating factor (G-CSF) therapy for 2 weeks and prophylactic dose of co-trimoxazole (5 mg/kg/day). Since there was not much improvement in cell counts, G-CSF was gradually hiked to 5 μg /kg/day. After hiking of dose, her TLC started improving (supplemental figure S1). At 10 months of follow up, she has normal leukocyte counts and there has been no breakthrough infections.