MSUD

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder caused by deficiency of the branched-chain alpha-ketoacid dehydrogenase complex (BCKD). This multi-enzyme complex normally breaks down the branched-chain amino acids leucine, isoleucine, and valine. Most cases are autosomal recessive and result from mutations in genes encoding components of the BCKD complex, notably BCKDHA, BCKDHB and DBT; other related genes can be involved in less common variants. The enzymatic defect leads to accumulation of branched-chain amino acids and their corresponding keto acids in blood and urine, which can be toxic to the brain.

Clinical presentation ranges from the neonatal period to later childhood. In newborns, symptoms typically appear within the first days of life and include poor feeding, vomiting, irritability, lethargy, and a distinctive maple syrup-like odor in urine, sweat, or earwax. If untreated, MSUD can rapidly progress to encephalopathy, seizures, coma, respiratory distress, and death. Less common forms include intermittent or thiamine-responsive MSUD, with symptoms triggered by illness or fasting.

Diagnosis is usually prompted by newborn screening in many countries, which detects elevated levels of leucine, isoleucine, and valine and their metabolites, especially alloisoleucine. Confirmatory testing involves quantitative amino acid analysis in plasma and urine, urine organic acids, and genetic testing to identify mutations in BCKD-related genes or enzyme activity assays.

Management focuses on preventing catabolic crises and lowering brain leucine exposure. Acute treatment includes ensuring a non-catabolic state with adequate glucose, fluids, and electrolyte management, and sometimes hemodialysis to rapidly reduce leucine levels. Long-term treatment requires a lifelong diet restricting branched-chain amino acids under metabolic supervision, with careful monitoring of growth and development. L-carnitine supplementation is commonly used to aid excretion of toxic metabolites, and liver transplantation has been reported in severe cases. With early detection and adherence to treatment, many individuals achieve normal development, though prognosis worsens with delayed diagnosis or metabolic crises. The condition is rare, and the name derives from the sweet odor of affected urine.