Decreased TREC and KREC levels in newborns with trisomy 21

Area of Science:

• Immunology
• Genetics
• Neonatal Medicine

Background:

• Newborn screening (NBS) for severe combined immunodeficiency (SCID) is crucial for early intervention.
• Trisomy 21 (Down syndrome, DS) presents unique challenges in NBS due to associated T and/or B cell lymphopenia.
• A pilot NBS program in Russia aimed to detect severe T and B cell deficiencies using TREC and KREC measurements.

Purpose of the Study:

• Evaluate Down syndrome incidence in the Russian pilot NBS program.
• Assess TREC and KREC values in newborns with Down syndrome.
• Determine the potential of T/B lymphopenia screening to identify DS newborns.

Main Methods:

• Retrospective analysis of data from 202,908 newborns across eight Russian regions.
• Measurement of T-cell receptor excision circles (TREC) and kappa-deleting recombination circles (KREC).
• Comparison of TREC and KREC values between DS newborns and the general cohort.

Main Results:

• Identified 157 cases of trisomy 21, yielding a DS birth prevalence of 1:1,284.
• DS newborns exhibited decreased TREC values, comparable to extremely preterm infants.
• Significant differences in KREC values were observed in DS newborns compared to the general cohort, irrespective of gestational age.

Conclusions:

• The study suggests intrinsic abnormalities in T- and B-cell lineage development in newborns with Down syndrome.
• Increased awareness of immunological defects associated with DS is warranted.
• Continued follow-up and comprehensive support are essential for individuals with DS.