combined immunodeficiency due to CTPS1 deficiency

Combined immunodeficiency due to CTPS1 deficiency is a very rare primary immunodeficiency disorder that affects the immune system by impairing the ability of activated T- and B-cells to proliferate. The condition is caused by changes in the CTPS1 gene, a critical gene involved in immune cell function. It typically presents in early childhood with recurrent viral and bacterial infections, including those from Epstein-Barr virus and varicella zoster virus. In view of its very rare occurrence, it is estimated to affect fewer than one person in a million.

Clinically, individuals with this condition show a spectrum of immunological abnormalities. Characteristic findings include a consistently reduced capacity for antigen-specific T cell proliferation, decreased specific antibody responses, and diminished levels of certain immunoglobulins such as IgG and IgG2. Patients often experience recurrent viral infections as well as sino-pulmonary bacterial infections, and other laboratory features such as an inverted CD4:CD8 ratio may be noted. It is important to recognize that not all individuals experience every feature, and the severity can vary considerably.

This condition is caused by pathogenic variants in the CTPS1 gene. In normal physiology, CTPS1 plays an essential role in the proliferation of immune cells after activation. The condition is inherited in an autosomal recessive pattern, which means that an affected individual inherits one altered copy of the gene from each parent. This condition is more common when parents share a common ancestor, as both are more likely to carry the same rare genetic variant, making carrier testing an important consideration for families with shared ancestry.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved or foundational therapies specifically linked to this condition. Treatment is tailored to the individual and often involves a multidisciplinary team working to address infectious complications and maintain overall health. Genetic counseling is recommended to help families understand the implications of the autosomal recessive inheritance pattern and to discuss family planning options. Patients should discuss treatment options with their healthcare team to determine which supportive interventions may be most appropriate for their specific circumstances.

The long-term outlook for individuals with combined immunodeficiency due to CTPS1 deficiency can vary widely, with outcomes depending on the severity of immunological impairment and access to comprehensive supportive care. With current standards of care, many individuals can experience periods of relative stability, although recurrent infections and complications may occur. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and immunology specialists who can provide ongoing guidance and help navigate treatment and monitoring strategies.

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.