Severe combined immunodeficiency: From its discovery to the perspective.

Severe combined immunodeficiency (SCID) is impaired in lymphocyte development and function. Affected children have extreme susceptibility to infections, which are fatal in the first year of life without treatment. The estimate of incidence is one in approximately 50,000 live birth. The first series of diseases were described in 1950s, and all patients died in infancy. The first transplant for SCID was carried out in 1968, and it has been described that SCID patients could be treated by hematopoietic stem cell transplantation (HSCT) since then. Adenosine deaminase and common gamma chain were identified to be causative genes for SCID in 1972 and 1993, respectively. SCID arises from a variety of genetic defects. The early intervention of healthy SCID infants without infections affords higher survival rate, and newborn screening (NBS) was suggested. T-cell receptor (TCR) exicision circles (TRECs) are circular DNA formed from the leftover fragment generated from the TCR rearrangement. TRECs can be measured from a small aliquot of DNA such as Guthrie card by quantitative PCR. SCID patients lack TRECs, and TRECs quantification is useful for NBS for SCID. NBS for SCID have been already carried out in most of the Unite States, and the early introduction is desired in Japan to save SCID children.