A Pediatric Case Series of Autoimmune Lymphoproliferative Syndrome (ALPS): A Single-Center Experience

Introduction Autoimmune lymphoproliferative syndrome (ALPS) is an inborn error of immune dysregulation. A defect in lymphocyte apoptosis leads to their accumulation and the survival of autoreactive B lymphocytes. Main characteristics of the disease are lymphoproliferation (lymphadenopathy and/or organomegaly) and autoimmunity (primarily autoimmune cytopenias). There are clinical criteria for the diagnosis, and in most cases, genetic diagnosis is also possible (mutations in FAS, FASLG, and CASP10 genes). Some patients meet clinical criteria for ALPS, but genetic defects are still undetermined (ALPS-U). Material and Methods This is a descriptive study with an observational case series from the Department of Pediatrics at the University Hospital Centre Zagreb, Croatia. We reviewed medical records from January 2012 until February 2026 of eight patients with ALPS and analyzed their demographic, clinical, laboratory, genetic, and treatment data. Results Eight children (four males, four females) with ALPS are being followed up in our center. Median age at diagnosis was 5 years (range 4 months–11 years). The most common clinical manifestation was splenomegaly (87.5%), followed by autoimmune cytopenias (62.5%) and lymphadenopathy (37.5%). All patients had elevated double-negative T cells and vitamin B12. One patient had hypogammaglobulinemia. Five patients have identical mutations in the FAS gene (four heterozygous, one homozygous), one patient has a mutation in the FASLG gene, one patient has ALPS-U (mutation not found), and for one patient, genetic analysis is pending. Sirolimus was used in three patients, improving their blood counts and leading to regression of lymphadenopathy and splenomegaly, and was well tolerated. Conclusion Due to the variable penetrance and heterogeneous clinical presentation, ALPS should be considered even in cases with atypical manifestations. Timely diagnosis is important, especially in the presence of immune cytopenias, to make tailored treatment decisions. Genetic testing of family members is necessary due to the increased risk of developing lymphoma in all carriers of the mutation.