Maple syrup urine disease: Characteristics of diagnosis and treatment in 45 patients in Chile

Am J Med Genet C Semin Med Genet. 2021 Sep;187(3):373-380. doi: 10.1002/ajmg.c.31933. Epub 2021 Jul 21.


Maple urine syrup disease (MSUD) is an autosomal recessive disorder characterized by deficient activity of the branched-chain alpha ketoacid dehydrogenase (BCKAD) enzymatic complex due to biallelic variants in the alpha (BCKDHA) or beta (BCKDHB) subunits or the acyltransferase component (DBT). Treatment consists in leucine (LEU), isoleucine (ILE), and valine (VAL) (branched-chain amino acids) dietary restriction and strict metabolic control. to determine the characteristics of the Chilean cohort with MSUD currently in follow-up at Instituto de Nutrición y Tecnología de los Alimentos, during the 1990-2017 period Retrospective analytical study in 45 MSUD cases. Measured: biochemical parameters (LEU, ILE, and VAL), anthropometric evaluation, and neurocognitive development. In 18 cases undergoing genetic study were analyzed according to the gene and protein location, number of affected alleles, and type of posttranslational modification affected. Then, 45 patients with MSUD diagnosis were identified during the period: 37 were alive at the time of the study. Average diagnosis age was 71 ± 231 days. Average serum diagnosis LEU concentrations: 1.463 ± 854.1 μmol/L, VAL 550 ± 598 μmol/L and ILE 454 ± 458 μmol/L. BCKDHB variants explain 89% cases, while BCKDHA and DBT variants explain 5.5% of cases each. Variants p.Thr338Ile in BCKDHA, p.Pro240Thr and p.Ser342Asn in BCKDHB have not been previously reported in literature. Average serum follow-up LEU concentrations were 252.7 ± 16.9 μmol/L in the <5 years group and 299 ± 123.2 μmol/L in ≥5 years. Most cases presented some degree of developmental delay. Early diagnosis and treatment is essential to improve the long-term prognosis. Frequent blood LEU measurements are required to optimize metabolic control and to establish relationships between different aspects analyzed.

Keywords: BCKDHA; BCKDHB; DBT; MSUD; leucine; neurocognitive development.

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / genetics
  • Alleles
  • Chile
  • Humans
  • Maple Syrup Urine Disease* / diagnosis
  • Maple Syrup Urine Disease* / genetics
  • Maple Syrup Urine Disease* / therapy
  • Retrospective Studies


  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)