Newborn Screening for Primary Immunodeficiencies: The Gaps, Challenges, and Outlook for Developing Countries.

Area of Science:

• Immunology
• Genetics
• Public Health

Background:

• Primary immunodeficiency diseases (PIDs) are inherited disorders increasing susceptibility to infections, autoimmunity, and cancers.
• PIDs are significantly under-diagnosed globally, particularly in high-consanguinity populations, leading to increased morbidity, mortality, and economic burden.
• Current newborn screening (NBS) methods using T-cell receptor excision circles (TRECs) and KREC ()]s are limited in scope and accessibility, especially in developing nations.

Purpose of the Study:

• To highlight the challenges and knowledge gaps in diagnosing and managing Primary Immunodeficiency Diseases (PIDs).
• To emphasize the need for early diagnosis through improved newborn screening (NBS) and clinical awareness.
• To advocate for country-specific TREC and KREC norms and local management guidelines.

Main Methods:

• Review of current diagnostic approaches for PIDs, including newborn screening (NBS) techniques.
• Analysis of challenges in PID diagnosis and management, particularly in resource-limited settings.
• Discussion of the necessity for clinical expertise and public awareness in PID detection.

Main Results:

• Under-diagnosis of PIDs is prevalent, with significant disparities between estimated and reported cases.
• Newborn screening (NBS) using TRECs and KRECs shows promise for early detection of severe PIDs but faces implementation hurdles.
• Existing NBS programs may miss certain PIDs, necessitating clinical vigilance and expertise.

Conclusions:

• Bridging knowledge gaps and establishing country-specific screening norms are essential.
• Developing local management guidelines and enhancing physician training are critical for improving PID care.
• Raising public awareness and conducting region-specific research are vital for addressing the global PID burden.