by Dr. Cathy van Rooyen
PATHCHAT Edition No. 5
Please contact your local Ampath pathologist for more information.
Why Screen for Severe Primary Immunodeficiencies?
Newborn screening for severe primary immunodeficiencies involving T- and B-lymphocytes enables early detection and treatment, potentially saving lives.
- Severe Combined Immunodeficiency (SCID) and X-linked Agammaglobulinemia (XLA) are hallmark conditions.
- Babies with SCID appear healthy at birth but will not survive beyond one year without treatment.
- Bone marrow transplant before three months has the highest success rate in curing SCID.
- XLA patients are at high risk for live vaccines (e.g., oral polio), which can lead to fatal infections.
- Early diagnosis can prevent vaccine complications and enable timely immunoglobulin replacement therapy to prevent severe infections.
Global Screening & the Need for Implementation in South Africa
- SCID and XLA are rare (1:35,000 – 1:100,000 live births), but early detection is cost-effective compared to long-term treatment costs.
- More than 30 U.S. states have mandatory neonatal screening for SCID with excellent outcomes.
- Many European countries have implemented screening, with the EU developing guidelines.
- South Africa currently lacks a national policy for screening.
- South African newborns receive live vaccines (BCG and polio) before hospital discharge, placing undiagnosed immunodeficient babies at even higher risk.
- Parental awareness is critical, and parents should have the option to screen their newborns before administering live vaccines.
How Does the Screening Work?
Ampath has implemented a qualitative real-time PCR assay that detects:
- T-cell receptor excision circles (TRECs): Best marker for functional T-cell production by the thymus.
- Kappa-deleting receptor excision circles (KRECs): Best marker for functional B-cell production by the bone marrow.
The screening test combines both TRECs and KRECs in a single PCR test, providing:
- Near 100% sensitivity
- 99.9% specificity
Who Should Be Screened?
1. All newborns (preferably before live vaccine administration).
2. Babies with a family history of severe primary immunodeficiency affecting B- or T-cells.
3. Neonates or older children where a severe primary immunodeficiency is suspected.
Specimen Requirements for Testing
- EDTA Blood Sample (Avoid dilution if collected from an intravenous line).
- Dried Blood Spot on a Guthrie card obtained via heel prick.
Limitations of the Screening Test
- False positives may occur in premature babies (<37 weeks gestation).
- If the initial screen is positive in a premature baby, the test should be repeated at 37 weeks corrected gestation.
Contact for Clinical Queries
For more information, please contact:
🔹 Dr. Cathy van Rooyen
📞 Tel: 012 678 0613/6
📧 Email: vanrooyenc@ampath.co.za
🔹 Dr. Sylvia van den Berg
📞 Tel: 012 678 0613/7
📧 Email: vandenbergs@ampath.co.za
CPD Questions
1️⃣ Newborn screening using TRECs can be used to identify babies with severe combined immunodeficiency (SCID).
- a. True
- b. False
2️⃣ Newborn screening using KRECs can be used to identify babies with primary agammaglobulinemia (XLA).
- a. True
- b. False
3️⃣ Which of the following conditions may cause a false positive screening test for SCID?
- a. Inborn errors of metabolism
- b. Prematurity ✅
- c. Congenital hypothyroidism
- d. Selective IgA deficiency
- e. Rhesus incompatibility