Atypical clinical presentation of primary hemophagocytic lymphohistiocytosis with a novel perforin1 gene mutation

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic disease characterized by abnormal or impaired function of cytotoxic T cells and natural killer cells leading to an exaggerated but ineffective immune response. We report a 3-year-old boy who is the only common son of a nonconsanguineous couple from Honduras without any history of hemophagocytic lymphohistiocytosis or other hematologic disorders in any of his half-siblings. He first presented to the emergency department with left leg pain. He underwent a left inguinal hernia repair 4 days prior to his initial presentation. He had several subsequent visits to the ER with abdominal pain, emesis, and headaches and was admitted when his symptoms did not resolve. On admission, he was found to have splenomegaly; elevated C-reactive protein, indirect bilirubin, C3 fraction; and pancytopenia. Bone marrow aspirate revealed paucicellular trilineage hematopoiesis with rare atypical histiocytic cells and no evidence of malignancy. An unequivocal diagnosis of HLH could not be made at that time, but was strongly considered. The patient’s neurologic status progressively deteriorated leading to brain death. Postmortem genetic analysis showed the patient to be a compound heterozygote with a 681 C > T (R232C) mutation and a novel Perforin1 missense mutation 659 G > A (G220D).