2009 Southern Regional Meeting Abstracts

Case Report: Purpose of Study: Case review of three brothers with X-Linked Agammaglobulinemia (XLA) caused by bruton's tyrosine kinase (BTK) gene mutation with atypical laboratory findings.
Methods Used: A retrospective chart review was used to describe cases of three brothers with recurrent sinopulmonary infections.
Summary of Results: LM presented at age 6.5 years with pneumonia. His history was significant for Kingella kingae osteomyelitis (18 months) and a previous episode of pneumonia (6 years). Immunologic workup revealed low absolute circulating B cells, absent IgM (<10 mg/dL), and normal IgG, IgA, and IgE. Pre and post vaccination titers revealed a normal response to diptheria and tetanus but no response to 14/14 pneumococcal serotypes. LM was started on monthly intravenous immunoglobulin (IvIg) and later switched to subcutaneous immunoglobulin (ScIg) therapy. LM, now 9 years old, has had no infections since starting immunoglobulin therapy.
KM presented at age 2 years after bilateral pressure equalization tubes (PET) placement. His history included chronic rhinorrhea, 1 episode each of pneumonia and bronchiolitis, and recurrent otitis media. KM’s immunologic testing revealed low absolute B cells, no response to pneumococcal vaccine, absent IgM, and normal IgG, IgA, and IgE. KM, now 4 years old, has continued to have recurrent otitis media requiring a second set of PET and antibiotics despite monthly IvIg.
BM presented with recurrent otitis media and gastroenteritis requiring hospitalization at age 16 months. BM had low absolute B cells, absent IgM, and normal IgG, IgA, and IgE. BM was started on IvIg therapy and has done well. Genetic testing for XLA was obtained on the brothers and sequencing revealed a 167T>C mutation in the BTK gene causing an Ile56Thr missense mutation (previously described). A fourth brother has had no clinical recurrent infections and normal BTK gene sequence. Maternal BTK gene profile is pending.
Conclusions: XLA is a rare humoral immunodeficiency due to BTK gene mutations resulting in a paucity of circulating B cells and low-absent serum immunoglobulins. To our knowledge, we are the first to report a family cohort of XLA with an isolated low IgM in the presence of normal IgG, IgA, and IgE.