Hemophagocytic Lymphohistiocytosis Associated with Synergistic Defects of AP3B1 and ATM Genes: A Case Report and Literature Review

Hemophagocytic lymphohistiocytosis (HLH) is an overwhelming immune system activation that manifests as hyperinflammation and life-threatening multiple organ failure. However, the clinical manifestations of the systemic inflammatory response in sepsis and fulminant cytokine storm caused by HLH macrophage activation are very similar and difficult to distinguish. HLH triggered by two novel gene defects manifesting with multiorgan dysfunction syndrome (MODS) and distributive shock has not been reported. A 14-year-old male patient was hospitalized with a high fever, his condition deteriorated rapidly, accompanied by cytopenia, shock, and MODS, and he was subsequently transferred to our intensive care unit (ICU) for symptomatic and organ-supportive treatments. Laboratory indicators of cytopenia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, high soluble CD25, low natural killer (NK) cell cytotoxicity, and hemophagocytosis in the bone marrow confirmed the diagnosis of HLH. Molecular genetic analysis revealed that two novel heterozygous gene mutations in AP3B1 (c.3197 C > T) and ATM (c.8077 G > T) might have accounted for the onset. After treatment, the patient’s condition successfully improved. This case report demonstrates the timely determination of underlying triggers and critical care supports (supportive and etiological treatment) of HLH related to the improved outcome.