We present a unique and unusual case of a male patient diagnosed with two coexisting and typically unassociated X-linked conditions: he was initially diagnosed with X-linked agammaglobulinemia (XLA) followed by a diagnosis of X-linked chronic granulomatous disease (XCGD) and an as of yet unpublished hypomorphic gp91phox variant in the CYBB gene. The latter was tested after the finding of granulomatous gingivitis. Hematopoietic stem cell transplant (HSCT) was performed due to severe colitis and nodular regenerative hyperplasia (NRH) of the liver. Following transplant, complete donor engraftment was observed with the restoration of a normal oxidative burst and full restoration of normal levels of circulating, mature CD19+ B cells. This case is singular in that it does not involve a contiguous gene syndrome in which deleted genes are in close proximity to either BTK and CYBB, which has been previously reported. To our knowledge, this is the first reported case of XLA and XCGD co-existing in a single patient and of having both inborn errors of immunity successfully treated by HSCT.

Background: Pediatric heart transplant recipients are at risk for complications from prolonged exposure to immunosuppressive drugs, possibly worsened due to over‐immune suppression in patients with pre‐existing immune abnormalities.Methods: This was a retrospective, single‐center pediatric cohort study and review of baseline immune evaluation in patients referred for heart transplant. Referrals included were from January 1, 2021, to June 31, 2022.Results: Fifty‐one patients were referred during the time period with a median age of 5 years (ranging 1 month‐20 years). Twenty‐seven total patients were transplanted. Given a lack of standardized immune evaluation, results were focused on lymphocyte quantitation, functional testing when available, and T‐cell subsets. Outcome measures focused on the number of infections and episodes of rejection requiring treatment. In total, 44.4% of patients experienced rejection, and the mean number of infections in the first 12 months post‐heart transplant was 2.1 (range 0–7 total infections).Conclusions: Baseline immune evaluation showed general T and B cell lymphopenia, without a clear connection between outcome differences for the number of infections or episodes of rejection requiring treatment. This small study demonstrated some differences in immune function in patients prior to heart transplant but was inadequately powered to draw conclusions about the effects of immunosuppression on post‐transplant outcomes.

Septins are a conserved family of hematopoietic cytoskeletal regulators. We report two full-term male siblings with a stop-loss variant in the X-linked SEPTIN6 gene who tested positive on SCID newborn screening and presented with myeloid tetraploidy, congenital neutropenia, absent circulating B cells, and variable T cell lymphopenia despite a normal percentage of naive T cells. In the proband, neutropenia was unresponsive to G-CSF with undetectable antineutrophil antibody. Both siblings had hypersegmented myeloid forms and tetraploidy with subsequent development of trisomy 8. One sibling had monosomy 7. Mature and progenitor B cells were markedly decreased to absent; rare plasma cells were present. Mature myeloid forms and plasma cells accumulated in the marrow leading to peripheral neutropenia and B cell lymphopenia. Matched sibling myeloablative HSCT resulted in full disease correction and minimal-to-no GVHD. In xenograft studies, altered SEPTIN6 function led to reduced early lymphoid progenitor cells, demonstrating that SEPTIN6 plays a critical role in lymphocyte development, representing a new inborn error of immunity.