Related Experiment Video
Updated: Jun 17, 2026
One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure
Published on: June 25, 2010
Reproductive Carrier Screening Detects Early Actionable Metabolic Conditions
Christian M Parobek1, Roni Zemet1, Vivienne Souter2
1Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX, USA; Baylor College of Medicine, Department of Obstetrics and Gynecology, Houston, TX, USA.
Insights
Reproductive carrier screening (RCS) can detect early actionable metabolic conditions (EAMCs) prenatally. This approach aids in early intervention, potentially reducing disease severity for newborns.
Area of Science:
- Genetics
- Metabolic Disorders
- Reproductive Health
Background:
- Early actionable metabolic conditions (EAMCs) are severe disorders with available early interventions.
- These conditions are not consistently included in newborn screening panels.
- Prenatal detection via reproductive carrier screening (RCS) offers a potential avenue for early intervention.
Purpose of the Study:
- To evaluate the clinical utility of detecting EAMC gene variants prenatally using RCS.
- To assess the carrier frequencies and theoretical affected pregnancy rates for EAMCs.
Main Methods:
- Identified 110 EAMCs from 113- and 275-gene carrier panels.
- Determined carrier status for EAMCs in 54,119 women undergoing RCS (2022-2024).
- Calculated theoretical affected pregnancy rates based on observed carrier frequencies.
Main Results:
- Carrier frequency for any EAMC was 1 in 6 (113-gene panel) and 1 in 4 (275-gene panel).
- Theoretical affected pregnancy rates were 0.07% (113-gene panel) and 0.08% (275-gene panel).
- Prevalent EAMCs included phenylketonuria, congenital adrenal hyperplasia, Wilson disease, Smith-Lemli-Opitz syndrome, and MCADD.
Conclusions:
- RCS enables prenatal detection of EAMCs.
- Early detection through RCS facilitates timely intervention.
- This can potentially reduce morbidity associated with certain metabolic disorders.
Purpose:
Early actionable metabolic conditions (EAMCs) are disorders that are often severe but have early interventions that can improve clinical outcomes. EAMCs are not universally included on newborn screening panels. We studied the clinical utility of detecting EAMC gene variants prenatally using reproductive carrier screening (RCS).
Methods:
We identified EAMCs from the 113 ACMG-recommended carrier panel and a 275-gene carrier panel. The carrier status for these EAMCs was determined in a cohort of women who underwent RCS between 2022 and 2024. Observed carrier frequencies were used to calculate theoretical affected pregnancy rates.
Results:
110 EAMCs were identified. Among 54,119 individuals, the carrier frequency for any EAMC was 1 in 6, using the 113-gene panel, and 1 in 4, using the 275-gene panel. Assuming random pairing, the theoretical affected pregnancy rates were 0.07% with the 113-gene panel and 0.08% with the 275-gene panel. The most prevalent EAMCs in this cohort were phenylketonuria (MIM:261600, 1 in 41), congenital adrenal hyperplasia (MIM:201910, 1 in 57), Wilson disease (MIM:201910, 1 in 63), Smith-Lemli-Opitz syndrome (MIM:270400, 1 in 75), and medium-chain acyl-CoA dehydrogenase deficiency (MIM:201450, 1 in 80).
Conclusion:
RCS facilitates detection and early intervention, which may reduce associated morbidity for certain metabolic disorders.
