Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder typically manifesting in childhood and characterized by chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. This study examines 6 Brazilian pediatric patients treated at our immunology and hematology divisions.
This retrospective review analyzed the medical records of 6 pediatric patients with heterozygous germline pathogenic or likely pathogenic variants in the gene FAS (c.676+1G>C, c.748C>T:p.Arg250*, c.778G>C:p.Asp260His). Regarding family history, all parents were asymptomatic. However, the mother of P1 and P2 (sisters) and the father of P4 carried the same variants as their children, while other parents were untested. Median age at probable clinical diagnosis, based on ESID 2019 criteria, was 8.4 years (range: 1.16–16.83 years), while genetic confirmation occurred at a median age of 12 years (range: 1.75–20.75 years). Symptoms onset occurred at a median age of 1 year (range: 0.58–3.75 years), with autoimmune cytopenia (n = 4) (ITP: n = 2; AIHA: n = 1; Evans' syndrome: n = 2) and benign chronic lymphadenopathy (n = 2). During follow-up, all patients developed chronic lymphoproliferation (lymphadenopathy: n = 5; splenomegaly: n = 4) and autoimmune cytopenias (AIHA: n = 5; ITP: n = 3; neutropenia: n = 2). Patients P1 and P2 presented with AIHA; three patients had cytopenias affecting two cell lineages. P3 exhibited cytopenia across all three hematopoietic lineages. At the time of ALPS suspicion, all patients exhibited elevated vitamin B12 levels and increased TCRαβ+ DNT cells. Four patients had hypergammaglobulinemia, while two had normal IgG levels for their age. Two patients reported allergic manifestations: P3 with recurrent urticaria and P6 with both recurrent urticaria and allergic rhinitis. Prior diagnoses included Castleman syndrome (P2), leishmaniasis, and acute lymphocytic leukemia (P3). Two patients underwent splenectomy before receiving an ALPS diagnosis. One patient initially treated with MMF transitioned to Sirolimus due to uncontrolled cytopenia, and another developed oral ulcers while on Sirolimus, which improved with laser treatment. All patients were stable and alive by study's end.
Recognition of clinical and laboratory features of ALPS is essential for early diagnosis and can significantly impact management and improve survival outcomes.
