X-linked Agammaglobulinemia of Bruton

Epidemiology and Etiology:

· Mutations in Btk (B-cell tyrosine kinase)

· Associated with the antigen receptor complex of pre-B and mature B cells

· Failure of pro-B and pre-B cells to mature into B cells

· B cell maturation stops after the rearrangement of the heavy chain genes

· Light chain genes are not rearranged and therefore not produced

· Free heavy chains are found in the cytoplasm

· T cell mediated reactions are entirely normal

· Males almost exclusively (X-linked)

· 6 months to 2 years presentation

· Maternal immunoglobulins are depleted at ~6mo

·

Common sites:

· Recurrent bacterial infections

· Respiratory tract

· Sinusitis

· Pharyngitis

· Otitis media

· Bronchitis

· Pneumonia

· Viral infections

· Gastrointestinal tract

· CNS via the blood

· Arthritis (35%)

Gross features:

·

Histologic features:

· Germinal centers are underdeveloped or rudimentary

· Pre-B cells in bone marrow are present in normal numbers

· CD19+, membrane immunoglobulins -

· Plasma cells absent

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· Btk gene is on Xq21.22

Other features:

· B cells absent or markedly decreased in peripheral blood

· Immunoglobulin levels in serum depressed

· Plasma cells absent

· Recurrent bacterial infections

· Haemophilus influenza

· Streptococcus pneumonia

· Staphylococcus aureus

· Viral infections

· Enteroviruses

· Echovirus

· Poliovirus (ex. live immunization)

· Coxsackievirus

· Protozoal infections

· Giardia lamblia

· Autoimmune diseases occur with increased frequency

· Arthritis

· Dermatomyositis

· Treatment is replacement immunoglobulin therapy

· Without treatment, most patients succumb to infection in infancy or early childhood

· With treatment, most reach adulthood

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.