Methods: Chart review of flow cytometry results, clinical lab results, and lung pathology are presented.
Results: A 13-year-old male with Kabuki syndrome presented with recurrent otitis media, immune thrombocytopenic purpura, and psoriasis. Workup for ITP (platelets 27 K/uL) revealed panhypogammaglobulinemia (IgG 241 mg/dL, IgA <5 mg/dL, IgM 65 mg/dL). Further evaluation showed deficient vaccine titers to mumps, tetanus, diphtheria and pneumococcal antigens. Lymphocyte subsets revealed a low CD4 T-cell count (314/mm3; nl 500-1300), low total memory (7.8/mm3; nl 50-200) and switched memory B-cells (1.3/mm3; nl 30-110). HRCT of the chest and abdomen revealed mediastinal lymphadenopathy; bronchiectasis; bilateral, lower-lobe predominant ground glass nodular abnormalities and splenomegaly. Lung biopsy showed follicular bronchiolitis, lymphocytic interstitial pneumonia, and non-necrotizing granulomas; immunohistochemistry showed a CD4 T-cell predominant infiltrate (CD4>CD8) with a smaller B-cell population. Collectively, these findings are consistent with GLILD. Infectious workup (CMV, EBV, AFB, fungus and routine bacterial cultures) was negative.
Conclusions: This is the first case report of a patient with Kabuki syndrome due to a KMT2D mutation and with biopsy-proven GLILD. This case illustrates that GLILD is not a complication limited to CVID. In fact, GLILD is well described in an increasing number of monogenic defects associated with immunodeficiency and immunodysregulation such as CTLA4 haploinsufficiency, LRBA deficiency and hypomorphic RAG1 mutations.