IKAROS Associated Immunodeficiency and Thrombotic Thrombocytopenic Purpura

Pathogenic variants in IKZF1 (IKAROS) are linked to immunodeficiency, malignancy, and immune dysregulation. We describe a family with a rare IKZF1 variant presenting with humoral immunodeficiency and thrombotic thrombocytopenic purpura (TTP). A non-consanguineous family was clinically monitored; clinical, immunological, and genetic data (exome sequencing and segregation analysis) were collected. Two siblings developed recurrent infections and relapsing TTP with low ADAMTS13 activity and anti-ADAMTS13 antibodies. Both harbored a heterozygous missense IKZF1 variant (c.487C>T; p.His163Tyr). Other relatives were tested negative. This expands the IKZF1-related disorder spectrum to include TTP with variable immune manifestations.