Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

Lauren Gunderman; Jeffrey Brown; Sonali Chaudhury; Maurice O'Gorman; Ramsay Fuleihan; Aaruni Khanolkar; Aisha Ahmed

doi:10.3390/biomedicines11030959

Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

Biomedicines. 2023 Mar 21;11(3):959. doi: 10.3390/biomedicines11030959.

Authors

Lauren Gunderman^{1

2}, Jeffrey Brown^{2

3}, Sonali Chaudhury^{2

4}, Maurice O'Gorman^{5

6}, Ramsay Fuleihan⁷, Aaruni Khanolkar^{8

9}, Aisha Ahmed^{1

2}

Affiliations

¹ Division of Allergy and Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
² Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
³ Division of Gastroenterology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
⁴ Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
⁵ Department of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.
⁶ Division of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
⁷ Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Irving Medical Center, New York Presbyterian Morgan Stanley Children's Hospital of New York, New York, NY 10032, USA.
⁸ Department of Pathology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
⁹ Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Abstract

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agammaglobulinemia (XLA) followed by a diagnosis of X-linked chronic granulomatous disease (XCGD) and an as of yet unpublished hypomorphic gp91phox variant in the CYBB gene.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.

Keywords: BTK; HSCT; X-linked agammaglobulinemia; X-linked chronic granulomatous disease; XLA; multi-genetic diagnosis.

Publication types

Case Reports

Grants and funding

GFT901460 (955620)/Jeffrey Modell Foundation