Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease

Abstract

Background

Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease‐causing mutations can affect the BCKDHA, BCKDHB, and DBT genes encoding for the E1α, E1β, and E2 subunits of the multienzyme branched‐chain α‐keto acid dehydrogenase (BCKDH) complex. In the present study, novel pathogenic variants in BCKDHB and DBT genes were identified in three Vietnamese families with MSUD.

Methods

Three newborn patients from three unrelated Vietnamese families were diagnosed with MSUD at the Metabolic Clinic, National Hospital of Pediatrics. Blood samples of 11 relatives from two generations of the three families diagnosed with MSUD were analyzed using exome and Sanger sequencing analyses.

Results

Novel pathogenic variants in BCKDHB (c.1103C>T, c.989A>G, and c.704G>A), and DBT (c.263_265delAAG) genes were identified in three pediatric patients with MSUD.

Conclusions

We have identified novel pathogenic variants in the MSUD‐related genes in the pedigree of the three patient's families. Our findings expand the mutational spectrum of MSUD and provide the scientific basis for genetic counseling for the patient's families.

Abstract

Novel mutations from patients with MUSD.