Hemophagocytic Lymphohistiocytosis (HLH) is a potentially fatal systemic disorder that may be primary or secondary. It results in overactivation and excessive proliferation of T cells and macrophages. Primary HLH is a associated with inheritance of a gene mutation.
Inheritance: autosomal recessive (rare autosomal dominant inheritance has been reported)
Onset of symptoms usually occur infancy or in early childhood but can occur in utero or in adolescence/adulthood.
Gene mutations associated with primary HLH:
(1) STX11 (6q24.2), encodes cytoplasmic protein syntaxin 11
(2) PRF1 (10q22.1), encodes perforin (expressed in CD8+ T-cells and NK cells)
(3) UNC13D (17q25.1), encodes cytoplasmic protein Munc13-4
(4) STXBP2 (19p13.2), encodes cytoplasmic protein Munc18-2
Other inherited disorders can mimic secondary HLH:
(1) immune disorders associated with hyperinflammatory response to infection
(2) inborn errors of metabolism
(3) immunodeficiencies
