Thiamine-responsive maple syrup urine disease missed by newborn screen: A case report

Abstract

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by a deficiency of the branched-chain α-ketoacid dehydrogenase (BCKAD) complex. It is classified into four subtypes: classic, intermediate, intermittent, and thiamine-responsive. We report a case of a female infant who presented with global developmental delay at 8 months of age. Plasma amino acid analysis revealed markedly elevated levels of leucine (1863 μmol/L), isoleucine (790 μmol/L), valine (1011 μmol/L), and alloisoleucine (427 μmol/L). The patient demonstrated marked improvement in biochemical markers, increased tolerance of dietary leucine intake, and developmental progress following thiamine supplementation. This case highlights a novel thiamine-responsive MSUD genotype and emphasizes the importance of recognizing this treatable subtype, the therapeutic potential of high-dose thiamine, and the possibility of false-negative results in newborn screening.

Keywords

• Maple syrup urine disease (MSUD)
• Branched chain α-ketoacid dehydrogenase (BCKAD) complex deficiency
• Thiamine-responsive MSUD
• Thiamine pyrophosphate