# Expert consensus on the combined screening of genes and biomarkers for neonatal diseases

## TL;DR

Experts in China propose a standardized framework for combining genetic and biomarker screening in newborns to improve early diagnosis and treatment of inherited metabolic disorders.

## Contribution

A multidisciplinary consensus framework for combined genetic and biomarker newborn screening in China, including 154 disease-causing genes and validated methodologies.

## Key findings

- 154 disease-causing genes covering 67 inherited metabolic disorders were prioritized based on treatability and early onset.
- A combined screening approach using dried blood spots and next-generation sequencing was validated for diagnostic accuracy.
- Standardized workflows for sample collection, result interpretation, and dual reporting were established for clinical implementation.

## Abstract

Newborn screening (NBS) through disease biomarkers has significantly reduced severe outcomes of congenital disorders. Moreover, exploratory newborn genetic screening programs are increasingly being implemented. This consensus, developed by multidisciplinary experts, aims to standardize the combined screening of genes and biomarkers for neonatal diseases in China, balancing ethical, technical, and clinical considerations.

This consensus synthesizes evidence from peer-reviewed literature (PubMed, CNKI, etc.) up to 2024 and integrates clinical experiences from multidisciplinary experts in neonatology, genetics, and laboratory medicine, focusing on disease biomarker-based NBS, newborn genetic screening, and the clinical utility of combined screening.

The consensus defines principles for combined screening: (1) disease/gene selection: 154 disease-causing genes covering 67 inherited metabolic disorders (e.g., amino acid metabolism disorders, organic acid metabolism disorders), prioritized by treatability, onset age (< 5 years), and cost-effectiveness; (2) methodology: integrating dried blood spot biomarker analysis with next-generation sequencing-based targeted capture (coverage > 300 ×), validated by MLPA/Sanger and long-range sequencing for complex variants (e.g., CYP21A2, SLC25A13); and (3) operational workflow: standardized workflows for informed consent, sample collection/delivery, and result interpretation, with dual reporting of marker and genetic findings within 15 days. Positive cases require family verification and/or other genetic sequencing techniques.

This consensus establishes a practical framework for integrating marker and genetic screening, aiming to improve diagnostic accuracy and achieve rapid and effective interventions, thereby saving lives and reducing the occurrence of severe complications. Implementation requires interdisciplinary collaboration and ongoing quality control to maximize clinical utility.