haemophagocytic lymphohistiocytosis, familial, type 3

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haemophagocytic lymphohistiocytosis, familial, type 3

A rare autosomal recessive, genetically heterogeneous disorder (OMIM:608898) characterised by immune dysregulation with hypercytokinaemia and defective natural killer cell function.

Clinical findings
Fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenaemia; neurologic abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. Haemophagocytosis is a prominent feature, as is a non-malignant infiltration of macrophages and activated T-cells in lymph nodes, the spleen and other organs.

Molecular pathology
Caused by defects in UNC13D, which encodes a protein that plays a role in cytotoxic granule exocytosis in leukocytes and is required for both granule maturation and granule docking, as well as for priming at sites of immune interactions.