X - linked agammaglobulinemia (XLA: X-linked agammaglobulinemia; Bruton agammaglobulinemia, congenital agammaglobulinemia, X - linked agammaglobulinemia type 1 -AGMX1-; immunodeficiency type 1 -IMD1-) Gene BTK
X - linked agammaglobulinemia (XLA: X-linked agammaglobulinemia) is a process that affects the immune system and occurs almost exclusively in males. Those affected have very few B cells and present a failure in the heavy chains of immunoglobulins. Consequently, they are very likely to develop infections produce few antibodies. XLA affects children tend to be healthy the first two months of life to be protected by antibodies transferred from the mother. Thereafter, when antibodies received from the mother begin to decline, suffering from recurrent infections. The most common infections are ear (otitis), lung (pneumonia), eye (conjunctivitis), sinus (sinusitis), caused by extracellular bacteria. There are also frequent gastrointestinal infections (chronic diarrhea) caused by bacteria or some protozoa (Giardia intestinalis). However, they are not vulnerable to virus infections by being controlled by Tc cells (CD8 +), except those caused by Enterovirus.
This process is caused by alterations in gene BTK (Bruton agammaglobulinemia tyrosine kinase), located on the long arm of chromosome X (Xq21.33-q22). This gene encodes the BTK (Bruton Tyrosine Kinase), important for the development of B cells and normal functioning of the immune system protein, so that mutations in the BTK gene by preventing the development of a normal BTK protein, affecting immunoglobulin synthesis. They described over 600 different mutations, most resulting in the absence of BTK protein. On other occasions, they cause a change in a protein amino acid which carries an abnormal BTK protein is rapidly degraded in the cell. Some individuals with XLA have deletions that remove one end of the BTK gene and neighboring genes, such as the TIMM8A gene. When the gene is affected TIMM8A DDON syndrome (Deafness Dystonia-Optic Neuropathy-) characterized by hearing loss, vision problems, and intellectual impairment -demencia- occurs, and muscle tension -distonía-, or difficulty of motor coordination (ataxia). In these cases the victims have infections that characterize the KLA syndrome with the manifestations of DDON syndrome.
The inheritance of this disease is X - linked recessive Being located the BTK gene on the X chromosome, one of the two sex chromosomes, males have only one X chromosome, the only altered copy of the gene is sufficient to cause the illness. In females, having two X chromosomes, the / s itself / s mutation / s has / have to occur in both copies of the gene to cause the disease, which is highly unlikely. Therefore, the process is more common in men than in women. A feature of this process is that parents do not pass on to their sons. About half of the cases have no family history of XLA. In most cases affected, the mother carries an altered copy of the gene without showing the disease. Carriers do not have immune system abnormalities associated with XLA, but pass the altered gene to their children. In other cases, the mother is not a carrier and the affected individual has a new mutation in the Btk gene, which was not in their parents.
Tests in IVAMI: in IVAMI perform detection of mutations associated conagammaglobulinemia X - linked (XLA), by complete PCR amplification of the exons of the BTK gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).