Two Years of Expanded Newborn Screening in Russia: High-Throughput Detection of Inherited Metabolic Disorders by Tandem Mass Spectrometry with Next-Generation Sequencing Confirmation

TL;DR

Russia expanded newborn screening for metabolic disorders, detecting 1 in 2900 cases with high-throughput methods and genetic confirmation.

Contribution

The study reports the first nationwide outcomes of expanded newborn screening in Russia using MS/MS and NGS confirmation.

Findings

Phenylketonuria was the most common inherited metabolic disorder detected (1 in 4600 live births).

Regional and ethnic variations were observed, such as high tyrosinemia type 1 in Chechen Republic.

NGS was crucial for resolving complex cases like dual diagnoses and heterozygous carriers.

Abstract

In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements.

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