A novel PRF1 gene mutation in a fatal neonate case with type 2 familial hemophagocytic lymphohistiocytosis

초록

Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondaryform (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorderthat occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatalneonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newbornpresented with severe sepsis-like features and required mechanical ventilation and continuousvenovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absenceof intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular geneticanalyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutationin PRF1, that is, c.65delC (p.Pro22Argfs*2) and c.1090_1091delCT (p.Leu364Glufs*93). Clinical andgenetic assessments for FHL are required for neonates with refractory fever and progressive multipleorgan failure, particularly when there is no evidence of microbiological or metabolic cause.

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