Early diagnosis of maple syrup urine disease using polymerase chain reaction-based mutation detection.

Background: Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by defective activity of the branched-chain alpha-ketoacid dehydrogenase enzyme complex. Early diagnosis and management of MSUD are imperative for preventing permanent neurological impairments. In the Philippines, a 4.7 kb deletion in the dihydrolipoamide branched-chain transacylase E2 (DBT) gene has been commonly identified in MSUD patients. Polymerase chain reaction (PCR) amplification of a junction fragment between intron 10 and exon 11 has been used to detect this deletion. The purpose of the present paper was to use PCR-based mutation detection of the deletion mutation to diagnose MSUD in neonates in order to provide proper diagnosis and effective treatment.

Methods: A region encompassing exon 11 and the junction fragment of the E2 (DBT) gene was PCR amplified from genomic DNA prepared from two neonates at risk for MSUD.

Results: PCR amplification of both exon 11 and the junction fragment from one of the neonates demonstrated that this case was a heterozygous carrier of the deletion. Thus, normal feeding was started. For the other neonate, PCR amplification of the junction fragment was successful, whereas the region encompassing exon 11 was not amplified. This neonate was genotyped as homozygous for the deletion, and treatment for MSUD was provided immediately.

Conclusion: Examination of the deletion mutation in the E2 (DBT) gene facilitated early MSUD diagnosis and was beneficial for the determination of the proper course of treatment.