Name: Immunodeficiency 97 | Acronym: IMD97
Alt. names: Immunodeficiency, common variable, 23 | CVID23 | Immunodeficiency 97 with autoinflammation | PIK3CG deficiency

Gene: PIK3CG | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 2 | First reported in: 2019

Last updated on: 2023-03-31 05:34:36 by Xiao P. Peng

OMIM: 619802

Orphanet: -

MONDO: 0030717

DOID: -

ClinGen: Moderate (2023-07-18)

Thus far, only 2 unrelated patients with this condition have been described (PMID: 31554793, 33054089). The first patient presented with a chronic progressive history of immunodeficiency, immune dysregulation and inflammation (PMID: 31554793), while the second had a more hyperinflammation-dominant phenotype (PMID: 33054089). Both patients had lymphopenia, impaired T-cell responses to TCR stimulation, and elevated markers of systemic inflammation. The first patient suffered from recurrent sinopulmonary, ear, skin, and urinary tract infections since childhood, followed by the development of recurrent autoimmune cytopenias, infiltrative lung and GI disease, lymphadenopathy, splenomegaly, and eczema (PMID: 31554793). Her immunophenotyping was notable for hypogammaglobulinemia, eosinophilia, reduced memory B cells, reduced memory and effector CD8+ T cells, decreased Tregs, and Th1 polarization. The second patient did not have a significant infection history or evidence of non-malignant lymphoproliferation, but presented acutely with systemic inflammation reminiscent of secondary hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS)(PMID: 33054089). Her immunophenotyping showed reduced NK cell count and degranulation as well as diminished monocyte and neutrophil phagocytic ability.

The first patient described above developed recurrent autoimmune cytopenias requiring treatment with rituximab and immunoglobulin replacement (PMID: 31554793). The second patient's secondary HLH/MAS was responsive to anakinra and dexamethasone (PMID: 33054089). She was eventually tapered off steroids but kept on a maintenance dose of Anakinra (eventually decreased to 60 mg once daily) without any further inflammatory manifestations.