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A rare form of agammaglobulinemia, a primary immunodeficiency disease, and is characterized by variable immune dysfunction with frequent and recurrent bacterial infections and/or chronic diarrhea.
ORPHA:33110Classification level: Subtype of disorder
Fewer than 100 cases of autosomal inherited agammaglobulinemia have been reported to date.
Patients with autosomal agammaglobulinemia are not able produce adequate amounts of immunoglobulins (Ig) and are therefore at increased risk of developing infections. They often come to medical attention with a dramatic infection at less than 2 years of age. Sepsis, meningitis, pneumonia with empyema, pyoderma (associated with neutropenia), severe diarrhea and enteroviral infection are common. They are generally healthy between episodes of infection. Age of onset is variable but infections generally develop from six months of age. Common clinical signs include upper respiratory tract infections with otitis and sinusitis, and lower respiratory tract infections with pneumonia and bronchiolitis, as well as gastrointestinal tract infections such as gastroenteritis. Less common manifestations include sepsis, meningitis, septic arthritis, osteomyelitis, and pyoderma. Severe bacterial infections with lung or CNS involvement may cause serious morbidity or be life-threatening. Associated autoimmune disorders and neurological complications are also found in some cases.
The disorder is due to mutations in various genes involved in humoral immunity, including: IGHM (14q32.33), BLNK (10q23.2-q23.33), CD79A (19q13.2), CD79B (17q23), IGLL1 (22q11.23), PIK3R1 (5q13.1) and TCF3 (19p13.3) Common causative microorganisms include Streptococcus pneumonia, Haemophilus influenza, Staphylococcus aureus, Salmonella spp and Giardia spp and enterovirus.
Diagnosis is suspected on the basis of early susceptibility to severe recurrent or persistent infections. particularly if the parents are consanguineous or belong to an isolated population. Abnormal laboratory parameters include low immunoglobulin levels and low or absent peripheral blood mature B lymphocyte counts. Molecular genetic testing should be performed to determine the genetic defect and to confirm the diagnosis.
Differential diagnoses include X-linked agammaglobulinemia in male patients, myelodysplasia or congenital infections.
In patients with this form of agammaglobulinemia, autosomal recessive transmission is more common than autosomal dominant transmission. Genetic counseling should be provided to affected families.
Management and treatment
There is no curative treatment but good disease control can be achieved through consistent gammaglobulin therapy. This can be given intravenously (400-600 mg/kg every 3 to 4 weeks) or subcutaneously (100 mg/kg every week). Therapy should be started as early as possible. Some immunologists advocate chronic prophylactic antibiotics and treatment of acute infections should be prolonged and at maximal doses of antibiotics.
The prognosis depends on the age at diagnosis, compliance with therapy and the development of complications. Most patients on treatment can lead a normal life.