Gastrointestinal Manifestations in X-linked Agammaglobulinemia

Abstract

Purpose: X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in X-linked agammaglobulinemia (XLA), the spectrum of gastrointestinal manifestations has not previously been fully explored.

Methods: We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the United States Immunodeficiency Network, a national registry of primary immunodeficiencies.

Results: In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide ranging, and management strategies were diverse and mainly experimental.

Conclusions: Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients.

Keywords: BTK; Bruton’s agammaglobulinemia; GI manifestations; IBD; X-linked agammaglobulinemia; XLA; enteritis; gastrointestinal manifestations; inflammatory bowel disease.

Figure 1

Patient A: Index case — 23 month old boy. Patient B: 71 year old maternal grandfather. Patient C: Maternal first cousin who died at 18 months of age from infectious complications over 30 years ago. He was diagnosed with bilateral ear infections that progressed to sepsis requiring admission to the intensive care unit, where he suffered from fatal cardiac failure due to myocarditis/pericarditis.

Figure 2

A) Flow cytometry for Patient B showing decreased (but not absent) bruton tyrosine kinase (btk) expression in monocytes (CD14+). B) Table showing flow cytometric analysis for btk.