Published: 18 Jun 2025

ICD9: 270.3      ICD10: E71.0      ICD11: 5C50.D0

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder.
It gets its name from the distinctive sweet odor of the affected person's urine, which smells like maple syrup. This odor is also sometimes noticeable in the person's sweat and earwax.

Here's a breakdown of what you need to know about MSUD:

Cause:

MSUD is caused by a deficiency or absence of a group of enzymes called the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex.
This complex is essential for breaking down three branched-chain amino acids (BCAAs): leucine, isoleucine, and valine.
When the BCKDH complex doesn't function properly, these BCAAs and their toxic byproducts (ketoacids) build up in the blood. This accumulation damages the brain and other organs.

Genetics:

MSUD is an autosomal recessive genetic disorder. This means a person must inherit two copies of the mutated gene (one from each parent) to have the disease.
People who inherit only one copy of the mutated gene are called carriers. They don't have the disease themselves, but they can pass the gene on to their children.

Types of MSUD:

There are different types of MSUD, based on the severity of the enzyme deficiency:

Classic MSUD: The most common and severe form. The BCKDH complex is virtually non-functional.
Intermediate MSUD: The BCKDH complex has some residual activity, leading to milder symptoms.
Intermittent MSUD: Symptoms only appear during times of stress, illness, or increased protein intake.
Thiamine-responsive MSUD: Rare form where the BCKDH complex can be partially activated by large doses of thiamine (vitamin B1).

Symptoms:

Symptoms vary depending on the type of MSUD and the level of BCAA accumulation. Common symptoms include:

Maple syrup odor: In urine, sweat, and earwax.
Poor feeding: Infants may have difficulty sucking or refusing to eat.
Lethargy (extreme sleepiness):
Irritability:
Poor weight gain:
Muscle tone problems: Can range from being floppy (hypotonia) to rigid.
Seizures:
Developmental delays: If not treated promptly.
Coma: In severe cases.
Brain damage: Untreated MSUD can lead to irreversible neurological damage.

Diagnosis:

Newborn screening: In many countries, newborns are screened for MSUD using a blood test that measures BCAA levels.
Urine organic acids analysis: This test can detect the abnormal ketoacids in the urine.
Blood amino acid analysis: Measures the levels of BCAAs in the blood.
Genetic testing: Can confirm the diagnosis by identifying mutations in the genes that code for the BCKDH complex.

Treatment:

The goal of treatment is to reduce BCAA levels in the blood and prevent neurological damage. Treatment typically involves:

Special diet: A lifelong, carefully controlled diet that limits the intake of leucine, isoleucine, and valine.
Medical formula: A special formula that provides essential amino acids, vitamins, and minerals, while excluding or limiting BCAAs.
Frequent blood monitoring: To monitor BCAA levels and adjust the diet as needed.
Emergency treatment: During illness or stress, special measures may be needed to prevent BCAA levels from rising too high. This might involve IV fluids, special formulas, and sometimes dialysis.
Liver transplantation: In some cases, a liver transplant can provide a functioning BCKDH complex and allow for a more normal diet.

Prognosis:

With early diagnosis and consistent treatment, individuals with MSUD can live relatively normal lives. However, it is a lifelong condition that requires strict adherence to a special diet and regular medical monitoring. Without treatment, MSUD can lead to severe neurological damage, coma, and death.

In summary, Maple syrup urine disease is a rare but serious genetic disorder that requires early diagnosis and lifelong management. If you have concerns about MSUD, it's essential to consult with a healthcare professional or a genetic specialist.