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.