IKAROS deficiency is caused by a mutation in the IKZF1 gene, which plays a key role in the differentiation and development of lymphoid and myeloid cells, and negatively regulates cell proliferation. Mutations are classified according to protein expression as haploinsufficiency, dimerization defect, dominant-negative (DN), and gain-of-function; all are associated to varying degrees with susceptibility to infections, autoimmunity, allergy, and malignancy.
Female infant received the Bacillus Calmette–Guérin (BCG) vaccine at 10 days of life. At 3 and 7 months of age, she presented with bronchiolitis and pneumonia, requiring hospitalization for 89 days, mechanical ventilation, broad-spectrum antibiotics, and treatment for severe viral, bacterial, and fungal infections. She developed swelling at the BCG injection site and ipsilateral axillary lymphadenopathy. Lymphocyte subpopulations showed B and T cell lymphopenia; CD20: 0.5%, hypogammaglobulinemia, normal dihydrorhodamine. Complete blood counts revealed monocytopenia, eosinopenia, and neutropenia. Genetic testing on 07/08/2024 revealed IKZF1 c.476A>G (p.Asn159Ser). Currently 20 months old, she is undergoing hematopoietic stem cell transplant evaluation (father 50% HLA compatible); she is receiving maintenance-phase anti-tuberculosis therapy, prophylactic antibiotics, and intravenous immunoglobulin.
This case involves a DN IKAROS mutation with an early-onset, severe, and fully penetrant phenotype. Of the nine cases reported worldwide, one-third received BCG vaccination without documented adverse reactions; these patients show increased susceptibility to malignancy, with no reported associations with autoimmunity or atopy. Definitive treatment is hematopoietic stem cell transplantation. IKAROS mutations are associated with a broad spectrum of immunological phenotypes; reporting of such cases contributes to timely recognition and treatment of these conditions.
