ALPS Diagnosis: Different Phenotype in Child and Mother

Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and susceptibility to malignancy. We present two cases: mother and son with different phenotype at onset.A 7-year-old child presented with anemia, thrombocytopenia and splenomegaly. In his family history: born from non-consanguineous parents, his mother had a splenectomy due to hemolytic anemia of unknown cause. In the child, initial differential diagnosis ruled out infection or malignancy. Bone marrow aspirate had erythroid hyperplasia, giant metamyelocytes and bands and low thrombopoyesis. His immunological evaluation had hypergammaglobulinemia, elevated TCRαβ+-DNT cells (10%). ALPS was suspected and he started Prednisolone and Mycophenolate.A mutation in FAS gene was identified (exon 9, c.785T > A, p.Ile262Asn). His mother, a 45-year-old female presented with a history of lymphadenopathy. In her past medical history, she had hemolytic anemia and splenomegaly, a splenectomy was performed and the anemia resolved. Initial evaluation was started because breast cancer was suspected. Lymph node biopsy was performed where malignancy was ruled out, but unspecific inflammatory infiltrate was found. An immunological evaluation was performed. The first that was identified was the history of his son with ALPS (not specified by any other physician). Due to her history, the lymphoproliferation and anemia Sanger sequencing of her sońs mutation was performed. It revealed the same mutation and treatment was started. FAS gene with 85% frequency is the main etiological cause of genetically diagnosed patients with ALPS phenotype. The factors that determine the penetrance of clinical ALPS have not been entirely determined. Penetrance appears to be relatively associated with the location and type of the mutation and even varies in individuals carrying the same genetic mutation.