Affecting the immune system, various forms of SCID are estimated to affect one in 75,000 to 100,000 newborns.
A new study led by Newcastle University has identified the genetic changes that are responsible for rare childhood immune disorders that can leave newborns with little to no immune defence against infections.
Published in Science Immunology, the study involved experts from the 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 function of children’s immune systems and put them at risk of life-threatening conditions.
While the prevalence of Omenn syndrome is unknown, the various forms of SCID are estimated to affect one in 75,000 to 100,000 newborns.
Without urgent treatment, including stem cell transplants to replace the faulty immune system, most children affected will not survive their first year of life.
Researchers studied 11 children, two who had SCID and nine who had Omenn syndrome, across four families. Each child involved had inherited mutations that disrupted the function of the NUDCD3 protein, which had previously not been associated with the immune system.
In these disorders, the mutations in the NUDCD3 protein prevented the normal development of diverse immune cells needed to combat different pathogens by impairing a crucial gene-rearranging process known as V(D)J recombination, which is essential for generating the diverse T cell receptors and antibodies needed to recognise and fight pathogens.
Despite mice engineered with the same NUDCD3 mutation having milder immune problems, the team found that human patients faced severe, life-threatening consequences.
Two of the paediatric patients survived after receiving a stem cell transplant, which ultimately reinforces the importance of early diagnosis and intervention.
Dr Gosia Trynka, author of the study, Wellcome Sanger and science director at Open Targets, commented: “These diseases leave newborns essentially defenceless against pathogens that most of us can easily fend off.
“The identification of this new disease gene will help clinicians to make a prompt molecular diagnosis in affected patients, meaning they can receive life-saving treatments more quickly.”
