Various forms of SCID, which affect the immune system, are estimated to affect 1 in 75,000 to 100,000 newborns.
New research led by Newcastle University has identified a genetic change that causes a rare childhood immune disorder that can give newborns little or no immune defence against infection.
Published in Science ImmunologyThe study involved experts from Great North Children’s Hospital, the Wellcome Sanger Institute and their collaborators.
Severe combined immunodeficiency (SCID) and Omenn syndrome are two rare genetic disorders that affect the functioning of a child’s immune system and put them at risk of developing life-threatening conditions.
The prevalence of Omenn syndrome is unknown, but various forms of SCID are estimated to occur in 1 in 75,000 to 100,000 newborns.
Without urgent treatment, such as stem cell transplants to replace their failing immune systems, most infected children will not survive the first year of life.
The researchers studied 11 children across four families – two with SCID and nine with Omenn’s syndrome – all of whom had a genetic mutation that blocks the function of the NUDCD3 protein, a protein not previously linked to the immune system.
In these diseases, mutations in the NUDCD3 protein impair a key gene rearrangement process called V(D)J recombination, which is essential for generating the diverse T cell receptors and antibodies needed to recognize and fight pathogens, preventing the normal development of the diverse immune cells needed to fight different pathogens.
Although mice engineered to carry the same NUDCD3 mutation had milder immune problems, the team found that human patients faced severe, life-threatening outcomes.
Two of the children survived and underwent stem cell transplants, highlighting the importance of early diagnosis and intervention.
“These diseases leave newborns essentially vulnerable to pathogens that most of us can easily fight off,” said Dr Gosia Trinca, Wellcome Sanger study author and scientific director of Open Target.
“Identification of this new disease gene will enable clinicians to rapidly perform a molecular diagnosis on affected patients, enabling them to receive life-saving treatment more quickly.”
