At this point, genetic testing results became available and identified two mutations in MUNC13-4: a known pathogenic mutation 1389(+1) G > A, a splice donor site of intron 15, and a second previously unidentified mutation, 1847 A > G. This second mutation was located in the splice donor site of exon 20, and the A > G change at this position would likely cause splicing error. It was unclear if this represented a compound heterozygous mutation or if the two variants were on a single chromosome. Parental testing was initiated. Given the genetic results and her persistent symptoms, the laboratory and bone marrow evaluations for HLH were reconsidered. Investigations relevant to HLH before, during and after anakinra use were evaluated (Tables 1 and 2) . When compared to the initial assessment, there was subsequent marked reduction in natural killer (NK) cell function, CD107a upregulation and an elevation in soluble IL-2 (soluble CD25) receptor. Importantly, a drop in ANC ( Figure 2a ) and platelet count (Figure 2b ) was identified during the end of the anakinra trial. Children with active HLH have been noted to have elevated white cell and platelet counts initially that decrease over time [6] , as illustrated in our case. As a confounding feature, however, cytopenia is an uncommon but known side effect of anakinra. It is thus possible that addition of anakinra in our patient, with underlying MUNC 13-4 mutations, magnified the drop in platelet count and ANC that would have been seen with HLH alone. In addition, when ferritin was measured on the 15 th day of anakinra therapy, the level was 629 ng/mL (above the aforementioned acceptable limit of 500 ng/mL), whereas one day after anakinra treatment was terminated, the ferritin level increased to 7129 ng/mL ( Figure 2c ). IL-1 is known to increase the synthesis of ferritin subunits in vitro [7] . We hypothesize, therefore, that anakinra administration inhibited the surge of ferritin that would have otherwise been identified in association with clinical progression of HLH.