Combining newborn metabolic and DNA analysis for second-tier testing of methylmalonic acidemia.

ABSTRACT:

Purpose

Improved second-tier tools are needed to reduce false-positive outcomes in newborn screening (NBS) for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP).

Methods

We designed an assay for multiplex sequencing of 72 metabolic genes (RUSPseq) from newborn dried blood spots. Analytical and clinical performance was evaluated in 60 screen-positive newborns for methylmalonic acidemia (MMA) reported by the California Department of Public Health NBS program. Additionally, we trained a Random Forest machine learning classifier on NBS data to improve prediction of true and false-positive MMA cases.

Results

Of 28 MMA patients sequenced, we found two pathogenic or likely pathogenic (P/LP) variants in a MMA-related gene in 24 patients, and one p

SUBMITTER: Peng G 

PROVIDER: S-EPMC6416784 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature