Early identification of delayed-onset ADA deficiency: The case for expanded first-tier newborn screening

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Severe combined immunodeficiency (SCID) is a group of rare genetic disorders that affect the immune system.
• Newborn screening for SCID typically uses T-cell receptor excision circle (TREC) assays.
• Adenosine deaminase (ADA) deficiency is a specific genetic cause of SCID.

Purpose of the Study:

• To report on two cases of delayed-onset ADA deficiency missed by standard newborn screening.
• To advocate for enhanced newborn screening protocols for SCID.

Main Methods:

• Case report of two patients with delayed-onset ADA deficiency.
• Review of standard newborn screening protocols for SCID.

Main Results:

• Two patients with delayed-onset ADA deficiency were not identified by standard newborn screening.
• Standard screening missed the diagnosis until irreversible end-organ damage began to develop.

Conclusions:

• Current newborn screening for SCID may not detect all cases, particularly those with delayed onset.
• Expanding first-tier newborn screening to include purine profiling alongside TREC assays is recommended.
• Early diagnosis through comprehensive screening enables timely, curative treatment for ADA deficiency and prevents severe health consequences.