granulomatous disease, chronic, autosomal recessive, 5

Granulomatous disease, chronic, autosomal recessive, 5 is a multisystem condition characterized by a range of immune and inflammatory abnormalities. It is caused by mutations in the CYBC1 gene, which plays a key role in the proper functioning of the immune system through the regulation of neutrophil activity. The condition typically presents in childhood with a constellation of recurrent infections and inflammatory findings, although precise prevalence data is not available. Affected individuals experience a range of symptoms, and the presentation can vary from one person to another.

Clinically, affected individuals consistently exhibit decreased neutrophil oxidative burst, splenomegaly, pleural effusion, short stature, decreased total lymphocyte count, lymphadenopathy, fever, recurrent pneumonia, abscesses, granulomas, recurrent tonsillitis, and hemolytic anemia. These features are considered hallmark manifestations and often lead to the initial evaluation of the condition. In addition, a subset of individuals may experience gastrointestinal complications such as Crohn’s disease, anal fissure, perianal abscess, or ulcerative colitis, as well as other findings including lymphadenitis, onychomycosis, acute pancreatitis, pulmonary fibrosis, eczematoid dermatitis, nephrotic syndrome, oral ulcers, hepatosplenomegaly, and a positive rheumatoid factor. Not all individuals experience all features, and severity varies considerably.

The condition is caused by pathogenic variants in the CYBC1 gene, which is essential for the proper regulation of the immune system’s oxidative burst mechanism, a critical process in fighting infections. It follows an autosomal recessive inheritance pattern, meaning that an affected individual has inherited two altered copies of the gene, one from each parent. This inheritance pattern implies that parents may be carriers without showing symptoms, and there is a 25% chance in each pregnancy for the condition to manifest if both parents are carriers. Genetic counseling is recommended for families to understand the implications and to provide guidance on family planning.

Currently, management focuses on supportive care and symptom management as there are no approved treatments specifically for this condition. Therapy is individualized and involves a multidisciplinary team that may include immunologists, infectious disease specialists, and other clinicians as needed. Long-term management emphasizes regular surveillance to detect complications early and to monitor organ systems affected by the disease. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to help guide families through management and family planning considerations.

Outcomes for individuals with granulomatous disease, chronic, autosomal recessive, 5 are highly variable, with the severity and range of symptoms differing from person to person. With current standards of care and advances in supportive management, many individuals benefit from improved quality of life and stabilization of their symptoms over time, though some may experience progressive challenges. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and specialists experienced with this condition for personalized guidance and to explore available support resources, recognizing that severity and symptoms vary widely between individuals.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.