A new frame shift pathogenic variant (c.773dupT) in the BCKDHB gene caused MSUD in an infant from north of Iran

Objectives Inborn errors of metabolism (IEMs) result from pathogenic variants in genes involved in essential metabolic pathways. Newborn screening (NBS) using tandem mass spectrometry (MS/MS) has facilitated the early detection and diagnosis of IEMs, enabling timely medical intervention and improved clinical outcomes. This study introduces a novel pathogenic variant in the BCKDHB gene in a case of maple syrup urine disease (MSUD) diagnosed through the NBS program in northern Iran. Case presentation Dried blood spot samples from newborns were analyzed using MS/MS (Shimadzu LCMS-8045, Japan), which identified a consanguineous case suspected of having MSUD. The confirmatory HPLC test revealed elevated levels of threonine, valine, isoleucine, and allo-isoleucine, indicating MSUD. Genetic analysis identified a homozygous frameshift variant, c.773dupT (NM_183050.4, p.Leu260ThrfsTer12), in exon 7 of the BCKDHB gene. Conclusions The identification of novel pathogenic variants in MSUD patients, along with phenotype-genotype correlations, may predict the clinical severity of the variant and offer prognostic value, particularly for individuals with this specific variant.