Familial hemophagocytic lymphohistiocytosis (fHLH) is a group of disorders that make the immune system overly active, leading to uncontrolled inflammation.
The first signs of FHL2 (fHLH due to the PRF1 gene) often include a high fever, infections, an enlarged liver and spleen (hepatomegaly), and low blood cell counts (cytopenia). As the condition worsens, neurological problems can develop, such as seizures, muscle issues, paralysis, and even blindness. If untreated, the disease can lead to organ failure. People with this condition also have a higher risk of developing cancers like leukemia and lymphoma. While severe symptoms usually appear within the first few weeks or months of life, some people might not experience symptoms until later.
The condition can be cured by replacing the immune system’s cells with healthy ones from a donor through a procedure called allogeneic hematopoietic stem cell transplantation (HSCT). Patients also often need medications to treat infections, like antibiotics or antivirals, and some might require blood transfusions.
This form of fHLH is caused by pathogenic (disease-causing) variants in the PRF1 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance of having a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. Most people with FHL2 have two harmful changes in the PRF1 gene. However, a few cases have shown one harmful change in the PRF1 gene and another in a different gene linked to fHLH (this is called digenic inheritance).
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Written August 2024
