A distinct variant of intermediate maple syrup urine disease

M. C. Gonzalez-Rios, D. T. Chuang, R. P. Cox, K. Schmidt, K. Knopf, S. Packman

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Branched chain α‐ketoacid dehydrogenase (BCKAD) deficiency, or maple syrup urine disease (MSUD), can be categorized as classical, intermediate, intermittent or thiamine responsive, based on generally concordant in vitro BCKAD activity and severity of phenotype. We present clinical and enzymatic data on a boy with intermediate maple syrup urine disease, and suggest that he represents a novel category of mutation. He presented at age 10 months in ketoacidotic coma, with a history of irritability, poor feeding and growth and developmental delay. Branched chain amino acid restriction effected normal growth and developmental parameters by age 42 months. In contrast to previous patients with intermediate MSUD, his fibroblasts and fibroblast extracts failed to decarboxylate [1‐14C]‐α‐ketoisovalerate (KIV). The defect is not in mitochondrial transport of substrate, but rather in the catalytic activity of the E1 component of the BCKAD. Disrupted cells of the proband exhibited negligible BCKAD activity over a wide range of keto acid substrate concentrations, irrespective of the presence of added thiamine pyrophosphate (TPP). These results differ from the sigmoidal kinetics observed using classical MSUD extracts, and the hyperbolic kinetics with control preparations under the same assay conditions. We propose that the structurally altered enzyme possesses reduced but not negligible activity in vivo, and exists as an unstable complex in vitro under assay conditions used, even in the presence of added TPP.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalClinical Genetics
Issue number2
StatePublished - Feb 1985


  • Branched chain amino acids
  • branched chain keto‐acid decarboxylase
  • isoleucine
  • leucine
  • maple syrup urine disease
  • thiamine
  • valine

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A distinct variant of intermediate maple syrup urine disease'. Together they form a unique fingerprint.

Cite this