autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency is an inherited immune disorder that leaves the body poorly equipped to fight certain infections. Variants in the RORC gene disrupt a key immune signaling pathway, leading to an impaired response against mycobacteria and some fungi. Symptoms usually begin in infancy or early childhood when affected children develop severe or persistent infections that would not normally cause serious illness in healthy people. The condition is extremely uncommon, affecting fewer than one person in one million worldwide. Severity and symptoms vary widely between individuals, so the experience of one family may differ from another.

The most characteristic feature is invasive infection caused by the Bacille Calmette-Guérin (BCG) vaccine strain or environmental mycobacteria, a complication known as BCGosis that occurs in the vast majority of affected individuals. Many children also experience recurrent or chronic fungal infections, particularly persistent oral thrush and painful skin or nail infections. Less commonly, people develop recurrent aphthous ulcers in the mouth, enlargement of the liver or spleen, or other signs of widespread inflammation when infections are not promptly controlled. Not all individuals experience all features, and the frequency, severity, and combination of symptoms can differ considerably even among siblings with the same genetic change.

This condition is caused by pathogenic variants in the RORC gene, which provides instructions for making the RORgamma receptor important for the development of specific immune cells that defend the body against mycobacteria and fungi. Because the disorder follows an autosomal recessive inheritance pattern, an individual must inherit two altered copies of RORC, one from each parent, to be affected. Parents who each carry a single pathogenic variant are usually healthy but have a 25 percent chance with each pregnancy of having a child with the condition. The disorder tends to be more common when parents share a recent common ancestor, because relatives are more likely to carry the same rare genetic variant. Genetic counseling can help families understand carrier testing options and implications for other relatives.

Currently, management focuses on supportive care and prompt treatment of infections. Care teams often include immunologists and infectious disease specialists who may recommend long-term antimicrobial prophylaxis, aggressive treatment of breakthrough infections, and close monitoring for complications such as liver or spleen enlargement. In addition to treating active infections, regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Because treatment needs differ from person to person, individuals and families should work closely with their healthcare providers to develop a personalized management plan and to stay informed about emerging therapeutic options. Genetic counseling is recommended for affected families to discuss carrier testing and future family planning.

Outcomes depend on how quickly infections are recognized and treated, the overall severity of immune dysfunction, and access to specialized care. Some individuals remain stable with careful monitoring and early antimicrobial therapy, while others experience recurrent or severe infections that can be life-threatening. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with an immunologist familiar with this condition and with a genetic counselor who can guide ongoing care and reproductive planning.