Identification of a novel BCKDHA deletion causing maple syrup urine disease

- The study presents a novel 3021 bp genomic deletion in the BCKDHA gene causing classic maple syrup urine disease (MSUD).
- The results demonstrate that large BCKDHA deletions are present in patients with different geographic origin.
- Large genomic deletions should be considered as a potential cause of MSUD in cases where the molecular diagnosis cannot be established by standard sequencing.

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder of the catabolism of branched-chain amino acids. The disorder can be caused by mutations within any of the BCKDHA, BCKDHB, DBT and DLD genes encoding the branched-chain alpha-ketoacid dehydrogenase complex. The aim of the study was to identify the molecular genetic cause of classic MSUD in a male neonate reported by newborn screening on the fourth day of life. The genetic analyses involved polymerase chain reaction (PCR) and sequencing of the BCKDHA, BCKDHB, and DBT genes. The results showed that the patient was homozygous for a novel 3021 bp deletion within the BCKDHA gene including exon 4 (NG_013004.1:g.13869_16889del) of this gene. The lack of exon 4 causes a reading frame shift and a premature termination codon in BCKDHA exon 5 (NP_000700.1:p.Gly126ValfsTer3). This strongly suggests that the novel BCKDHA deletion is pathogenic and is the cause of classic MSUD in this patient.