MSUD is a rare genetic disorder that affects the body’s ability to break down certain amino acids. This can lead to serious health issues, including developmental delays and metabolic crises if not managed properly.
Parents can carry one copy of the gene that causes MSUD without symptoms. If both are carriers, each pregnancy has a 25% chance that the child will inherit two copies and develop MSUD.
Infants with MSUD may experience poor feeding, lethargy, and a distinctive sweet odor in their urine. Early diagnosis is crucial to managing the condition effectively.
Increasing awareness about MSUD helps in early detection and treatment. Understanding this disorder can support families in managing health and nutritional needs.
Maple syrup smell in urine and earwax – often the first noticeable sign
Poor feeding, loss of sucking reflex, and general feeding problems
Irritability, becoming listless, and developing a high-pitched cry
Episodes of rigidity alternating with periods of limpness
In variant types, this may be the first symptom noticed
Illness, infection, or fasting can trigger metabolic crisis episodes
MSUD is a genetic disorder caused by a defect in the enzyme needed to process certain essential amino acids. Without this enzyme, the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be broken down and will build up to toxic levels without treatment.
Each parent of a child with MSUD carries one abnormal gene for MSUD and one normal gene. Parents are called “carriers” and are not affected by the disorder as the normal gene is dominant (expressed). A child with MSUD has received an abnormal gene from each parent.
When both parents are carriers, there is a 1 in 4 chance with each pregnancy that the baby will receive an abnormal gene from each parent and develop MSUD; a 2 in 4 chance the baby will receive one abnormal and one normal gene, thus becoming a carrier of MSUD; and a 1 in 4 chance the baby will receive two normal genes. Persons with two normal genes cannot pass MSUD to their offspring.
Because a person with MSUD has two abnormal genes, a child born to that person will automatically be a carrier. However, the child will not have MSUD unless the other parent also has MSUD or is a carrier.
chance baby will develop MSUD
(receives abnormal gene from each parent)
chance baby becomes a carrier
(one abnormal, one normal gene)
chance baby is unaffected
(receives two normal genes)
Without proper enzyme function, these BCAAs build up to toxic levels.
Maple Syrup Urine Disease (MSUD) is primarily caused by mutations in the BCKDHA, BCKDHB, or DBT genes, which provide instructions for making the branched-chain alpha-ketoacids dehydrogenase (BCKDC) complex. The BCKDC enzyme is essential to break down branch chained amino acids (BCAA) found in protein-rich foods.
Variant of classic type. Higher enzyme activity allows greater leucine tolerance. However, when ill or fasting, reacts just like classic MSUD. Management similar to classic type. May not be detected until later in life.
Milder form. Often no symptoms until 12–24 months, usually triggered by illness or a sudden protein increase. During episodes, BCAA levels rise, a maple syrup odor appears, and metabolic crisis can occur. Between episodes, individuals can often tolerate a normal protein intake, though dietary management and monitoring of BCAA levels remain important. The clinical presentation can vary; some may escape detection on newborn screening, while others can have a perinatal crisis.
Rare type. Large doses of thiamine increase enzyme activity that breaks down leucine, isoleucine and valine. Only moderate protein restriction needed for this uncommon variant. Due to lack of detailed data, researchers are uncertain if this type of MSUD truly exists.