In those fulfilling HLH-2004 diagnostic criteria who had genetic testing, the majority had negative HLH gene panel testing (66.7%); however, we found that immunodeficiency (CTLA4 deficiency, RAS-associated lymphoproliferative disorder) was as common as mutations traditionally associated with HLH (LYST, XIAP). The gene discussed is CTLA4; the disease is lymphoproliferative syndrome.