Mutation in the FAS gene is the main cause of autoimmune lymphoproliferative syndrome (ALPS). It causes defective cellular apoptosis and clinically manifests by lymphoproliferation, increased risk of lymphoma and autoimmune diseases. Here, we report a case of ALPS-FAS initially manifested by multilineage cytopenia in a patient attended at the Children´s Hospital –Brasilia/Brazil.
Laboratory and clinical data were reviewed from medical records. FAS sequencing was done by Sanger method and protein expression measured by flow cytometry.
KRCS, male, 5yo, second child of consanguineous parents. No family history of immunodeficiency. At 3yo7mo he was hospitalized due to cutaneous rash, fever and pancytopenia. No infectious disease was identified. Bone marrow aspiration were negative for malignancy and the diagnosis of autoimmune hemolytic anemia was made, with response to oral corticoids. Due to the high levels of serum vitamin B12 and IgG, associated to lymphoproliferation and increased percentages of circulating CD3+TCRab+CD4-CD8-DNT cells (4%), ALPS was suspected. Genetic analysis confirmed FAS mutation c.748C>T p.R250*, which was inherited from his asymptomatic father (DNT=6.9%). Flow cytometry analysis showed low FAS expression on T cells of proband and his father. The mother and the sister have normal % of DNT (<1.5%).
The nonsense mutation FAS:c.748C>T results in a defective protein and its subnormal surface expression causing impairment in the apoptotic signaling pathway of lymphocytes. Although the proband and his father have the same mutation, they have different clinical manifestations. This is an intriguing query that could be related to environmental, other genetic factors or a trigger such as infections.