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Review
. 2022 Aug;63(1):22-35.
doi: 10.1007/s12016-021-08870-5. Epub 2021 Jul 9.

Agammaglobulinemia: from X-linked to Autosomal Forms of Disease

Melissa Cardenas-Morales  1 , Vivian P Hernandez-Trujillo  2   3
Affiliations
Review

Agammaglobulinemia: from X-linked to Autosomal Forms of Disease

Melissa Cardenas-Morales et al. Clin Rev Allergy Immunol. 2022 Aug.

Abstract

Interruptions or alterations in the B cell development pathway can lead to primary B cell immunodeficiency with resultant absence or diminished immunoglobulin production. While the most common cause of congenital agammaglobulinemia is X-linked agammaglobulinemia (XLA), accounting for approximately 85% of cases, other genetic forms of agammaglobulinemia have been identified. Early recognition and diagnosis of these conditions are pivotal for improved outcomes and prevention of sequelae and complications. The diagnosis of XLA is often delayed, and can be missed if patient has a mild phenotype. The lack of correlation between phenotype and genotype in this condition makes management and predicting outcomes quite difficult. In contrast, while less common, autosomal recessive forms of agammaglobulinemia present at younger ages and with typically more severe clinical features resulting in an earlier diagnosis. Some diagnostic innovations, such as KREC level measurements and serum BCMA measurements, may aid in facilitating an earlier identification of agammaglobulinemia leading to prompt treatment. Earlier diagnosis may improve the overall health of patients with XLA.

Keywords: Agammaglobulinemia; Bruton’s tyrosine kinase; Common variable immunodeficiency; Immunoglobulin replacement therapy; X-linked agammaglobulinemia.

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Conflict of interest statement

Vivian Hernandez-Trujillo reports conflict with Ad board for Takeda and CSL; Speaker for Takeda; Consultant for Takeda. Melissa Cardenas-Morales does not have any conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Criteria for probable diagnosis of agammaglobulinemia in patients with no genetic diagnosis ( adapted from https://esid.org/Working-Parties/Registry-Working-Party/Diagnosis-criteria)
Fig. 2
Fig. 2
Diagnostic criteria for X-linked agammaglobulinemia. Adapted from Winkelstein, Jerry A. MD; Marino, Mary C. MLS; Lederman, Howard M. MD, PhD; Jones, Stacie M. MD; Sullivan, Kathleen MD, PhD; Burks, A. Wesley MD; Conley, Mary Ellen MD; Cunningham-Rundles, Charlotte MD, PhD; Ochs, Hans D. MD X-linked agammaglobulinemia, report on a United States Registry of 201 Patients Medicine: July 2006—Volume 85—Issue 4—p 193–202 https://doi.org/10.1097/01.md.0000229482.27398.ad
See this image and copyright information in PMC

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