Definitive

Male patient with less than 2% CD19+ B cells and at least one of the following:

1. Mutation in Btk
2. Absent Btk mRNA on northern blot analysis of neutrophils or monocytes
3. Absent Btk protein in monocytes or platelets
4. Maternal cousins, uncles or nephews with less than 2% CD19+ B cells

Probable

Male patient with less than 2% CD19+ B cells in whom all of the following are positive:

1. Onset of recurrent bacterial infections in the first 5 years of life
2. Serum IgG, IgM and IgA more than 2SD below normal for age
3. Absent isohemagglutinins and /or poor response to vaccines
4. Other causes of hypogammaglobulinemia have been excluded (see Table)

Possible

Male patient with less than 2% CD 19+ B cells in whom other causes of hypogammaglobulinemia have been excluded (see Table) and at least one of the following is positive:

1. Onset of recurrent bacterial infections in the first 5 years of life
2. Serum IgG, IgM and IgA more than 2 SD below normal for age
3. Absent isohemagglutinins

Spectrum of disease

Most patients with XLA develop recurrent bacterial infections, particularly otitis, sinusitis and pneumonia, in the first two years of life. The most common organisms are S. pneumonea and H. influenzae. The serum IgG is usually less than 200 mg/dl (2g/L) and the IgG and IgA are generally less than 20 mg/dl (0.2g/L). Approximately 20% of patients present with a dramatic, overwhelming infection, often with neutropenia. Another 10-15% have higher concentrations of serum immunoglobulin than expected or are not recognized to have immunodeficiency until after 5 years of age.

Differential diagnosis

All other causes of hypogammaglobulinemia listed in Table:

1. Mu heavy chain deficiency
2. Lambda 5 deficiency
3. Igα deficiency

Other information

• Patient and Family Handbook For The Primary Immune Deficiency Diseases by IDF.
• X-Linked Agammaglobulinemia by The Jeffrey Modell Foundation (JMF).