combined immunodeficiency due to GINS1 deficiency

Combined immunodeficiency due to GINS1 deficiency is a severe immune disorder that also affects growth and development. Affected individuals exhibit markedly low lymphocyte and neutrophil counts, absent natural killer cells, and intrauterine growth retardation, with many also experiencing facial dysmorphism and short stature. The condition is caused by pathogenic variants in the GINS1 gene and is inherited in an autosomal recessive pattern, meaning that two copies of the abnormal gene are required. It is very rare, affecting fewer than one in a million people.

The clinical presentation is defined by characteristic features such as decreased total lymphocyte count, intrauterine growth retardation, and the absence of natural killer cells, which are consistently present. Early on, affected individuals often present with recurrent infections and signs of growth retardation that may be evident before and after birth. As the condition evolves, patients may develop additional features including abnormal facial shape, short stature, lymphadenopathy, and dermatologic issues such as eczematoid dermatitis, dry skin, and ichthyosis, while a subset may also experience diarrhea, microcephaly, or myelodysplasia. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the GINS1 gene, which plays a critical role in DNA replication and cell division. Disruption of its function adversely affects the development and function of immune cells as well as overall growth. It is inherited in an autosomal recessive manner, meaning that an affected individual inherits two copies of the altered gene, one from each parent. The condition is more common when parents share a common ancestor, as the likelihood of both carrying the same rare variant is increased.

Currently, management focuses on supportive care and symptom management rather than specific curative therapies. Treatment is tailored to the individual and typically involves a multidisciplinary team that provides ongoing surveillance to detect complications early. Regular monitoring of immune function, growth, and other system parameters is an essential part of long-term care. Genetic counseling is recommended for families to understand inheritance patterns and plan accordingly, and patients should discuss treatment options with their healthcare team to determine the most appropriate approach.

Outcomes vary depending on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals manage to live into adulthood, although the condition may progress, stabilize, or have a variable course among different patients. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition to obtain support and guidance for future planning.