Hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis

Other Names:Familial hemophagocytic lymphohistiocytosis; Familial erythrophagocytic lymphohistiocytosis; Familial histiocytic reticulosis; FHL; HLH

Hemophagocytic lymphohistiocytosis (HLH) is a condition in which the body makes too many activated immune cells (macrophages and lymphocytes). People with HLH usually develop symptoms within the first months or years of life. Symptoms may include fever, enlarged liver or spleen, cytopenia (decreased number of blood cells), and neurological abnormalities. HLH may be inherited in an autosomal recessive manner or it can have non-genetic causes in which case it is called acquired HLH. There are five subtypes of inherited HLH which are designated as familial HLH, types 1-5. Each subtype is caused by a change (mutation) in a different gene. The genetic cause of type 1 is currently unknown. Types 2-5 are caused by mutations in the PRF1 gene, the UNC13D gene, the STX11 gene and the STXBP2 gene, respectively. Treatment depends on a number of factors, including the severity of symptoms, the age of onset, and the underlying cause of the condition.

When HLH results from an inappropriate immune response to Epstein-Barr virus or another viral illness, it may be due to a separate genetic condition called X-linked lymphoproliferative disease (XLP). XLP is caused by a mutation in the SH2D1A or XIAP gene and is inherited in an X-linked manner.

The signs and symptoms of hemophagocytic lymphohistiocytosis typically develop during the first months or years of life. However, in rare cases, affected people may not show symptoms until later in childhood or even into adulthood. The features of this condition may include:

  • Fever
  • Enlarged liver and/or spleen
  • Skin rash
  • Lymph node enlargement
  • Breathing problems
  • Easy bruising and/or abnormal bleeding
  • Kidney abnormalities
  • Heart problems
  • Increased risk for certain cancers (leukemia, lymphoma)

Many people with this condition also develop neurologic abnormalities. The neurological symptoms vary but may include irritability, fatigue, abnormal muscle tone, seizures, neck stiffness, mental status changes, ataxia, blindness, paralysis, and/or coma.

Contact the Genetic and Rare Diseases (GARD) Information Center for more information on Hemophagocytic lymphohistiocytosis.


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