familial hemophagocytic lymphohistiocytoses
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, fatal disorder of early infancy.
sudden-onset fever
visceral lymphohistiocytic infiltration
meningeal lymphohistiocytic infiltration
hepatic anomalies
- hepatic failure
- hepatosplenomegaly
- hepatorenal failure
- portal infiltrates of T lymphocytes
- portal infiltrates of histiocytes
- periportal infiltrates of T lymphocytes
- periportal infiltrates of histiocytes
- activation of the hepatic mononuclear phagocytic system
- focal hemophagocytosis
- loss of interlobular bile ducts (biliary ductopenia)
- paucity of bile ducts (biliary ductopenia)
Loci
HLH1: at 9q21.3-q22
HLH2 at 10q21-q22: mutations in the gene encoding perforin (PRF1) (MIM.170280)
HLH3 at 17q25.1: mutations in the UNC13D gene (MUNC13-4)(MIM.608897)
HLH4 at 6q24: mutations in syntaxin-11 (STX11) (MIM.605014)
Differential diagnosis
Omenn syndrome (familial reticuloendotheliosis with eosinophilia) (MIM.603554)
Faisalabad histiocytosis (hemophagocytic lymphohistiocytosis with sensorineural deafness and joint contractures) (MIM.602782)
Griscelli disease: GS1 (MIM.214450), GS2 (MIM.607624), GS3 (MIM.609227)
References
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Wieczorek R, Greco MA, McCarthy K, Bonetti F, Knowles DM 2nd. Familial erythrophagocytic lymphohistiocytosis: immunophenotypic, immunohistochemical, and ultrastructural demonstration of the relation to sinus histiocytes. Hum Pathol. 1986 Jan;17(1):55-63. PMID: 3080365
Akima M, Sumi SM. Neuropathology of familial erythrophagocytic lymphohistiocytosis: six cases and review of the literature. Hum Pathol. 1984 Feb;15(2):161-8. PMID: 6698535