Abstract
Mutations in any one of several genes essential for T lymphocyte development and function cause human Severe Combined Immunodeficiency (SCID), a
heterogeneous group of monogenic inborn errors of immunity.
Newborns with SCID acquire multiple, persistent, and severe viral, bacterial, and
fungal infections shortly after birth and rarely reach their first birthday. SCID is a
pediatric emergency: with prompt diagnosis and treatment, essentially every baby with
SCID could be cured by hematopoietic stem cell transplantation or gene therapy.
Most SCID newborns appear normal and healthy at birth, but SCID is always a prenatal
disorder of the development of T lymphocytes, and it is already present at birth.
Therefore, SCID is detected by newborn screening through measurement of TRECs (T
cell receptor excision circles), which counts naïve T lymphocytes, already absent or
markedly reduced.
The vast majority of newborns worldwide are not yet screened for SCID. The
diagnostic approach and the ‘natural history’ of affected infants and their families are
now completely different depending on whether or not neonatal screening for SCID is
available, apart from the availability/unavailability of SCID therapies (hematopoietic
stem cell transplantation, etc.).
Keywords: B-cell, Bubble boy, Gene therapy, Genetics, Genotype, Hematopoietic stem cell transplantation, Immunodeficiency, Leaky mutation, Lymphopenia, Maternal engraftment, Newborn screening, NK-cell, Null mutation, Omenn syndrome, Phenotype, SCID, T-cell, Thymus, TRECs, Viral vector.
