Haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1) is a recently identified autoinflammatory disorder characterized by significant rheumatologic, immunologic, and hematologic manifestations. We present a case of SOCS1 haploinsufficiency in a 4-year-old girl with bone marrow failure.
We collected data from clinical records, genetic testing, and functional immune assays.
A 4-year-old female with no significant family history was referred to the immunology unit due to bone marrow aplasia. Her clinical course began at age 2 with immune thrombocytopenic purpura (ITP), which responded to intravenous immunoglobulin and corticosteroids. By age 3, she developed bone marrow aplasia, platelet refractoriness, recurrent fevers, gastrointestinal bleeding, and severe infections. Immunological workup revealed low IgM levels (-2 SD) prior to rituximab and normal lymphocyte subsets. Whole exome sequencing (WES) identified a heterozygous SOCS1 variant: NM_003745.2:c.295G>A, p.(Gly99Ser). Familial segregation analysis showed the mutation was de novo. A functional interferon (IFN) signature test revealed a markedly elevated IFN score of 64.5 (reference cutoff: 8.4, mean +2 SD). Based on these findings, treatment with the Janus kinase inhibitor (JAKi) ruxolitinib—targeting IFN-γ–mediated inflammation—was proposed.
This case underscores the importance of a multidisciplinary diagnostic approach and the role of comprehensive genetic evaluation in patients with atypical presentations of immune-mediated cytopenias. Early identification of monogenic immune disorders such as SOCS1 haploinsufficiency can guide targeted therapy and improve outcomes.
