Agammaglobulinemia is a rare inherited immunodeficiency disorder that is characterized by low (<2%) or absent mature B cells, leading to severe antibody deficiency and a large clinical presentation that varies among patients, such as severe bacterial infections, bronchiectasis, gastrointestinal infections, etc., associated or not with autoimmunity and inflammation. Agammaglobulinemia includes X-linked agammaglobulinemia (XLA), also known as Bruton’s disease, which is caused by a mutation in the Bruton tyrosine kinase (BTK) gene, and autosomal recessive or dominant agammaglobulinemia that has been reported to be caused by genes that affect B cells. This study aims to describe the clinical, immunological phenotype, and genetic results of patients with autosomal and X-linked agammaglobulinemia.
We report 47 patients diagnosed as autosomal or X-linked agammaglobulinemia. Each patient had clinical evaluation, immunological analysis (CBC), lymphocyte subpopulation assay (CD3, CD4, CD8, CD16, and CD19), and immunoglobulin dosage (IgA, IgG, IgM, IgE), and 29 of them also received genetic testing.
46.8% of the patients had X-linked agammaglobulinemia, while 53.1% had autosomal agammaglobulinemia. The average age at onset of symptoms was 11 months, and the average age at diagnosis was 43.75 months. The sex ratio was 4.87. 23.4% of the patients were born to consanguineous marriages, and 34% had a family history. Clinically, the patients presented with a variety of symptoms, with the most common being sinopulmonary infections (74.5%). Pneumopathy was seen in 42% of patients, gastrointestinal infections in 21%, and skin infections in 42.5%. Autoimmunity was observed in 8% of the patients. All patients had a low (<1%) or absent circulating B cell count, along with significantly reduced immunoglobulin levels. The average levels were 0.08 for IgA, 0.21 for IgM, and 0.77 for IgG. Genetic analysis of the 29 patients identified mutations in the BTK gene in 25 cases, while 3 patients had mutations in the IGHM gene. Additionally, 1 patient carried a double heterozygous pathogenic mutation in the SLC39A gene.
Although the percentage of autosomal agammaglobulinemia is generally low worldwide, in North African countries, it increases due to the high rate of consanguinity. Early identification and diagnosis of agammaglobulinemia is important in decreasing morbidity and mortality, as swift initiation of immunoglobulin replacement may help to prevent sequelae, such as life-threatening infections.
