Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of early infancy characterized by fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis, which represent the diagnostic criteria. 1, 2 In the absence of a specific marker, differential diagnosis may be difficult, especially in patients without familial recurrence. Mutations in PRF1, a gene relevant for cellular cytotoxicity mechanisms whose mutations result in impaired antiviral defense and dysregulation of the apoptotic mechanisms, have been first documented in patients with HLH (HLH2; Online Mendelian Inheritance in Man# 603553) by Stepp et al. 3

The same clinical picture is apparently shared by patients with HLH due to PRF1 mutations or any other cause. 4-6 Most patients develop HLH within the first few months of age. In the series of 122 patients collected by the International HLH Registry, most patients were diagnosed between 1 and 6 months. 1 Exceptions to this general rule have been observed, as in the past there have been reports of familial cases with an age at onset of up to 8 years. 1, 7 Furthermore it has been observed that the age at onset for affected siblings is usually comparable and often coincides; 1 discordant and later onset has been exceptionally reported. 8 Clementi et al4 reported a PRF1 mutation in a 6-year-old patient, an age at which onset of HLH is rarely observed, and discussed whether adult forms of HLH2 may exist. We report 2 siblings sharing the same mutations in the PRF1 gene, who developed HLH at 22 and 21 years, respectively.