Immunologic and genetic workup of HLH. Rapid immunologic testing (which may be performed in 1-3 days) may support a diagnosis of HLH and provide etiologic data, whereas gene sequencing (typically requiring 3-8 weeks) may define the underlying genetic cause. Measurement of NK cytotoxic function and sCD25 may also support the diagnosis of HLH but is not included in the diagram because abnormalities in these assays do not suggest specific genetic lesions. Of note, whereas an abnormal test suggests an underlying gene abnormality, a normal immunologic test does not preclude genetic testing. Genetic testing should be pursued until biallelic (or hemizygous) mutations are found or until all 5 genes (or 7, in the case of males) are assayed. LYST gene sequencing is not currently commercially available.