title: Atypical features of familial hemophagocytic lymphohistiocytosis.
abstract: Familial hemophagocytic lymphohistiocytosis (FHLH) is a rare, rapidly progressive disorder of early childhood characterized by uncontrolled activation of T cells and macrophages. Although perforin gene mutations have been described in a proportion of patients with FHLH, the genotype/phenotype correlation is still limited. Only a few patients with late onset clinical manifestations have been reported. The biochemical and immunologic alterations in the asymptomatic phase are not well known. We report on a family in which 2 fraternal twins both homozygous for a perforin mutation previously described as causative of the disease, markedly differed in phenotypic expression of FHLH. The twins also had a second novel heterozygous mutation. Natural killer (NK) activity was severely impaired in the patient and was normal in the asymptomatic fraternal twin. Our report highlights that FHLH may present after a long disease-free interval during which biochemical or immunologic alterations may be not evident, thus implying a role for interfering factors.
authors.affiliation: Department of Pediatrics, Unit of Immunology, Federico II University, via S Pansini 5, 80131 Naples, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Busiello
authors.forename: Marsilio
authors.initials: M
authors.lastname: Adriani
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Mario
authors.initials: M
authors.lastname: Galgani
authors.forename: Giorgia
authors.initials: G
authors.lastname: Fimiani
authors.forename: Rita
authors.initials: R
authors.lastname: Clementi
authors.forename: Matilde Valeria
authors.initials: MV
authors.lastname: Ursini
authors.forename: Luigi
authors.initials: L
authors.lastname: Racioppi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pignata
mesh_terms: D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005091:Exons / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D020014:K562 Cells; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D004247:DNA