What Is Maple Syrup Urine Disease Type Ib?

Maple syrup urine disease (MSUD) type Ib, caused by mutations in the BCKDHB gene, is an inherited metabolic disorder named for the characteristic maple syrup odor of an affected individual's urine. MSUD is caused by the lack of an enzyme needed to break down three amino acids (building blocks of proteins): leucine, isoleucine, and valine, which are collectively known as branched-chain amino acids. These amino acids are found in all foods containing protein. Without the needed enzyme, known as branched-chain ketoacid dehydrogenase (BCKAD) complex, these amino acids and their byproducts accumulate and cause damage to the body.

MSUD can be classified into four general types: classic, intermediate, intermittent, and thiamine-responsive. Classic MSUD is the most severe type. Individuals with other types exhibit milder symptoms but are prone to periods of crisis in which symptoms closely resemble classic MSUD. In all types of the disease, there is a risk of intellectual and physical disability.

Classic Type

The most common type, classic MSUD, is characterized by little or no BCKAD enzyme activity. Symptoms in infants with classic MSUD will appear in the first week of life. Within 12 to 24 hours or upon first consumption of protein, the infant's urine will take on a maple-syrup odor. Within several days, the infant will show poor feeding, vomiting, and irritability, followed by lack of energy, weight loss, seizures, muscle tone that alternates between stiff and limp, and swelling of the brain. If untreated, life-threatening coma or respiratory failure can occur within 7 to 10 days and death can occur within the first two months.

Upon any lapse of treatment, classic MSUD can cause brain damage. Individuals with the disease are particularly prone to crisis during illness, during infection, during fasting, or after surgery.

Intermediate Type

Individuals with intermediate MSUD have some BCKAD enzyme activity. Thus, intermediate MSUD is similar to the classic form but is less severe. Generally, individuals with this form can tolerate higher amounts of the amino acid leucine than those with the classic type. During periods of crisis, however, this tolerance drops and symptoms and risks are nearly identical to those of the classic type.

Intermittent Type

This form of the disease is rare. In individuals with intermittent MSUD, BCKAD enzyme activity is reduced but not absent. The onset of the disease may not occur until the first or second year of life. Symptoms are often episodic and are more likely to appear during illness, fasting, or periods of high protein consumption. As with the intermediate type, in times of crisis, risks and symptoms are similar to those of the classic form.

Thiamine-Responsive Type

Thiamine-responsive MSUD is distinct in that individuals with this form of the disease are expected to show a decrease in symptoms when treated with large doses of thiamine (vitamin B1). Studies suggest that this form exists; however, the evidence is not yet definitive.

How Common Is Maple Syrup Urine Disease Type Ib?

The worldwide prevalence of MSUD is estimated to be 1 in 185,000 individuals. MSUD type Ib is estimated to account for approximately 35% of all MSUD cases. It is most common among the Ashkenazi Jewish population, where the prevalence is approximately 1 in 37,000 individuals.

How Is Maple Syrup Urine Disease Type Ib Treated?

MSUD type Ib is primarily controlled by diet; patients control it primarily by eating only foods low in protein. This often means severe restrictions on meat, fish, eggs, dairy foods, whole grain flour, beans, and nuts. Often individuals with MSUD type Ib are given a special liquid formula that supplies nutrients without the amino acids they cannot digest. These dietary restrictions should begin immediately upon diagnosis and must continue for the individual's entire life.

Management is also key to proper treatment. Amino-acid levels in the blood should be monitored regularly by a physician. Blood-test findings can help to calibrate the diet and are particularly important during pregnancy for a mother with MSUD. Any swelling of the brain requires immediate medical attention. Illnesses should always prompt a consultation with a physician, as these are vulnerable periods for an individual with MSUD type Ib. He or she may need a special “sick-day diet” to avoid hospital stays.

Those with thiamine-responsive MSUD may be prescribed thiamine supplements. To date, no patients with any form of MSUD have been treated only with thiamine supplementation. Instead, a combination of thiamine supplementation and restriction of dietary protein intake has been used, which makes it difficult to determine the true impact of a thiamine-only treatment plan.

What Is the Prognosis for an Individual with Maple Syrup Urine Disease Type Ib?

If untreated, MSUD can be fatal. With early, careful, and lifelong treatment and a low-protein diet, individuals with MSUD type Ib can live healthy lives into adulthood and show normal growth and mental development. It is particularly critical to recognize the disease as soon as symptoms appear in order to avoid brain damage and mental disability. Despite careful treatment, some individuals with the disease will experience periodic flare-ups, particularly during times of illness. These episodes can lead to learning problems or intellectual disability and may be life-threatening.

Other names for
maple syrup urine disease type Ib

  • Branched-chain alpha-keto acid dehydrogenase (BCKAD/BCKD) deficiency
  • Branched-chain ketoaciduria
  • Maple syrup urine disease
  • Maple syrup urine disease (MSUD) type 1B


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  • Nellis et al., 2003, Mol Genet Metab, 80(1-2):189-95, PMID: 14567968
  • OMIM: Online Inheritance in Man, OMIM [248600], 2016, https://www.omim.org/entry/248600
  • Strauss et al., 2013, https://www.ncbi.nlm.nih.gov/books/NBK1319/