Maple syrup urine disease (MSUD)

Alternative names	Branched-chain ketoacid decarboxylase (BCKD) deficiency
About the condition	Maple syrup urine disease is an amino acid disorder. It is a hereditary disease that is caused by a missing enzyme needed to metabolise the branched-chain amino acids (leucine, isoleucine, and valine) found in protein. These amino acids accumulate in the blood and are toxic to the brain.
Inheritance	Autosomal recessive
Year screening started in WA	2005
Incidence in Australia	Approximately 1 in 100,000 births
Enzyme defect	Deficient activity of the enzyme complex involved in the oxidative decarboxylation of the alpha-keto acid derivatives of leucine, isoleucine, and valine.
Symptoms if untreated	MSUD usually causes problems very early in the newborn period, such as poor feeding, vomiting, lethargy, hypoglycaemia, seizures, opisthotonic posturing, and coma. If not treated, the disease soon leads to death. The infant's urine has a sweet maple syrup smell, which gives the condition its name. There are some less severe forms of the condition, the mildest of which may go undetected for months or years. These may be associated with intellectual disability.
Metabolites on bloodspot screening	Increased leucine and isoleucine Increased alloisoleucine (second-tier test)
Diagnostic tests	Plasma amino acids Urine organic acids BCKDHA, BCKDHB, and DBT gene analysis
Treatment	Early assessment and treatment are important and infants may need intensive care initially Leucine, isoleucine, and valine restricted diet Essential amino acid supplementation Evaluate for possible thiamine responsiveness
Screening issues	Mild forms of MSUD may be missed as the branched-chain amino acids may not be increased in the first weeks of life.