Maple syrup urine disease (MSUD) is an autosomal-recessive disorder of branched-chain amino-acid metabolism caused by deficiency of the branched-chain alpha-ketoacid dehydrogenase complex. Toxic accumulation of leucine and related metabolites can cause severe encephalopathy and seizures.
Classic neonatal MSUD
Babies with classic MSUD are usually normal at birth.
Without treatment, they develop poor feeding, lethargy, abnormal movements, apnoea, opisthotonus, seizures, cerebral oedema and coma over the first days of life.
The characteristic odour
A sweet maple-syrup or burnt-sugar odour can be detected in cerumen and later urine.
Absence of a noticed odour does not exclude the diagnosis.
Leucine toxicity
High leucine concentrations disturb brain amino-acid transport, neurotransmitter balance and cellular metabolism.
Rapid reduction of leucine is essential during metabolic crisis.
Seizures and abnormal movements
Severe intoxication can cause seizures, but dystonia, opisthotonus and characteristic “fencing” or “bicycling” movements can also occur.
Not every abnormal movement is necessarily epileptic.
Diagnosis
Plasma branched-chain amino acids and alloisoleucine are key diagnostic tests.
Alloisoleucine is one of the most sensitive and specific biochemical markers of MSUD.
Genetics
MSUD is caused by biallelic variants affecting components of the BCKD complex, including BCKDHA, BCKDHB and DBT.
Newborn screening
Many countries include MSUD in newborn screening.
Prompt treatment of screen-positive infants can prevent the catastrophic neonatal presentation.
Acute decompensation
Infection, injury, surgery and fasting can trigger rapid protein catabolism and dangerous leucine elevation even in previously stable individuals.
Acute illness plans are therefore essential.
Current acute-management principles
International 2026 guidance emphasises stopping catabolism, providing high-energy intake, maintaining protein synthesis and rapidly reducing toxic branched-chain amino acids.
Dialysis or haemofiltration can be used when leucine concentrations are dangerously high or neurological deterioration is severe.
Why dialysis alone is not enough
Removing leucine from blood does not stop ongoing release from body protein.
Successful treatment also requires reversing catabolism and promoting net protein synthesis.
Long-term treatment
Treatment usually involves carefully controlled dietary leucine intake with specialised branched-chain-amino-acid-free medical formula and supplementation of isoleucine and valine as needed.
Thiamine responsiveness
A minority of individuals have thiamine-responsive disease.
This should be determined under specialist metabolic supervision rather than assumed.
Liver transplantation
Liver transplantation can stabilise branched-chain amino-acid metabolism, allow a much less restricted diet and largely protect against future metabolic crises.
It does not reverse established neurological injury.
Epilepsy after metabolic injury
Some people develop persistent epilepsy following severe neonatal or later metabolic brain injury.
Others have seizures only during intoxication.
Worldwide access
Outcome depends heavily on newborn screening, specialist metabolic dietetics, access to emergency biochemical testing and intensive care.
These resources differ substantially between countries.
The central point
In MSUD, seizures can signal toxic leucine accumulation and cerebral oedema. The metabolic crisis itself must be reversed urgently.
Related reading
Sources
- GeneReviews — Maple Syrup Urine Disease
- 2026 international guidance — acute metabolic decompensation in MSUD
Medical note: metabolic decompensation in MSUD is a medical emergency.
Evidence checked: September 2026.