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

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