SUMMARY

 

          Autosomal agammaglobulinemia is quite rare compared to XLA. However, this diagnosis should be considered in male patients with agammaglobulinemia who do not have a btk mutation, females with agammaglobulinemia, or patients who have a family history consistent with autosomal recessive inheritance. To date, six forms autosomal agammaglobulinemia have been described involving proteins in the B-cell receptor or downstream signaling molecules.

 

1. Mu Heavy Chain Deficiency (IGHM - AR) Mutations in the heavy chain of the pre B-cell receptor can lead to arrest of B-cell development. The clinical phenotype of patients is very similar to XLA, although they can be more severe. Sinopulmonary infections, enteroviral encephalitis, Pseudomonas sepsis, chronic Giardia, and neutropenia have all been described. 

 

 

2. Lambda 5 Deficiency (IGLL1 - AR) Mutations in the surrogate light chain of the pre B-cell receptor can also lead to arrest of B-cell development. 

 

 

3. Ig alpha Deficiency (CD79A - AR) Ig alpha is part of a signal transducing complex that associates with the pre B-cell receptor. Mutations in Ig alpha lead to impaired signaling downstream from the pre B-cell receptor leading to arrest in B-cell development. 

 

 

4. Ig beta Deficiency (CD79B - AR) Along with Ig alpha, Ig beta is also part of a signal transducing complex that associates with the pre B-cell receptor. Mutations in Ig beta lead to impaired signaling downstream from the pre B-cell receptor leading to arrest in B-cell development. 

 

 

5. BLNK Deficiency (AR) BLNK is a downstream signaling molecule that is activated following B-cell receptor cross-linking. Mutations result in an arrest in B-cell development at the pro B-cell to pre B-cell stage.

 

 

6. LRRC8 Defiency (AD) Agammaglobulinemia has been reported in a patient who had a truncation of the Leucine-rich repeat-containing protein 8 gene. The patient also had minor facial abnormalities including hypertelorism, high arched palate, and low set ears. The exact function of this gene has not been elucidated.