How is Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency diagnosed?

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare genetic disorder characterized by an increased susceptibility to severe infections caused by certain types of bacteria, particularly mycobacteria. It is caused by mutations in genes involved in the immune system, leading to impaired immune responses against these pathogens.

Diagnosing MSMD due to partial STAT1 deficiency involves a combination of clinical evaluation, immunological testing, and genetic analysis. The process typically begins with a thorough medical history and physical examination to identify any signs or symptoms suggestive of MSMD. These may include recurrent or severe infections, particularly with mycobacteria, as well as a family history of similar infections.

Immunological testing plays a crucial role in the diagnosis of MSMD. This involves assessing the immune system's response to specific antigens or stimuli. One common test is the interferon-gamma release assay (IGRA), which measures the production of interferon-gamma by immune cells in response to mycobacterial antigens. A positive IGRA result suggests an impaired immune response and may indicate MSMD.

Genetic analysis is essential for confirming the diagnosis of MSMD and identifying the specific genetic mutation responsible. This typically involves sequencing the relevant genes associated with MSMD, such as the STAT1 gene. Genetic testing can be performed using a blood sample or other appropriate tissue samples. Identifying the specific mutation helps in understanding the underlying mechanism of the disease and can guide treatment decisions.

It is important to note that the diagnosis of MSMD due to partial STAT1 deficiency requires expertise in immunology and genetics. Therefore, it is typically carried out by specialized healthcare professionals, such as immunologists or clinical geneticists, in collaboration with laboratory geneticists.