When Neutropenia Hides a Genetic Disorder: A Case of ALPS Type 2 Due to CASP10 Mutation

Introduction Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder caused by impaired lymphocyte apoptosis. It is typically characterized by chronic nonmalignant lymphoproliferation, autoimmune cytopenias, and an increased risk of lymphoma. ALPS type 2, associated with CASP10 gene mutations, is an uncommon autosomal dominant variant that may present with mild or atypical features. Case Report We present the case of a male infant born September 2020, to non-consanguineous parents, with an unremarkable perinatal course. At one year of age, routine blood work unexpectedly revealed persistent neutropenia, accompanied by eczematous skin lesions. Clinical examination revealed normal somatic and neurodevelopmental parameters, with no evidence of hepatosplenomegaly or lymphadenopathy. Bone marrow aspiration demonstrated a reduced number of neutrophils and a predominance of eosinophils. Immunological evaluation revealed an IgA level at the lower limit of normal, with normal IgG and IgM levels. Lymphocyte immunophenotyping showed normal T cell subsets (CD3+, CD4+, and CD8+), along with a mildly decreased B cell count. The patient subsequently experienced recurrent febrile episodes that responded favorably to antibiotic treatment. Neutropenia persisted, while hemoglobin and platelet levels remained within normal ranges. His growth and neurodevelopment continued to progress appropriately. Genetic analysis revealed a heterozygous pathogenic variant in the CASP10 gene (c.1202_1208del, p.(C401Lfs*15)), confirming the diagnosis of autoimmune lymphoproliferative syndrome type 2 (ALPS-2). Autoimmune serologies were negative, and no clinical or radiological evidence of lymphoproliferation has been observed to date. Conclusion This case highlights an atypical and mild presentation of ALPS-2, revealed by isolated neutropenia. It underscores the importance of thorough evaluation in persistent unexplained neutropenia, even in the absence of classical ALPS features, to enable early diagnosis and appropriate genetic counselling.