What is Maple Syrup Urine Disease Type Ia?

Maple syrup urine disease (MSUD) is an inherited metabolic disorder named for the characteristic maple syrup smell of the affected individuals's urine. There are three genes that cause MSUD, but the symptoms are identical regardless of which gene is causing the disease. MSUD type Ia is caused by harmful genetic changes (mutations) in the BCKDHA gene. Individuals with MSUD are unable to break down substances known as branched-chain amino acids, or BCAAs. High levels of BCAAs are toxic to the body and cause the symptoms associated with MSUD. BCAAs are found in all foods containing protein.

MSUD can be classified into three general types: classic, intermediate, and intermittent. 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

Classic MSUD is typically observed in the first week of life. Within 12 to 24 hours of birth, the infant's urine will take on a "maple syrup" smell. Individuals who are unfamiliar with maple syrup describe the odor as similar to fenugreek. Within several days, the infant will show poor feeding; vomiting; and irritability. This is followed by symptoms including lack of energy; weight loss; seizures; a tense, arched posture; muscle tone that alternates between stiff and limp; and swelling of the brain. If untreated, life-threatening coma or respiratory failure could occur within 7 to 10 days. If untreated, classic MSUD can cause brain damage, and many untreated infants will die within the first few months. Individuals with the disease are particularly prone to crisis during illness, infection, or fasting, or after surgery. Older individuals with MSUD often experience attention-deficit/hyperactivity disorder, depression, or anxiety disorders.

Intermediate Type

Intermediate MSUD is similar to, but less severe than, the classic form. The age of onset varies, and individuals may not experience severe symptoms in the newborn period. Individuals with intermediate MSUD generally experience poor feeding and growth and often have developmental delay in infancy or early childhood. During times of crisis such as illness, infection, or fasting, or after surgery, the symptoms of intermediate MSUD are nearly identical to those of the classic type.

Intermittent Type

This form of the disease is rare. Children with intermittent MSUD generally have normal feeding and growth with no developmental delays. Individuals typically only experience symptoms 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.

There is another type of MSUD referred to as "thiamine-responsive," where individuals are mildly affected and can be treated with high levels of thiamine to reduce or eliminate symptoms. However, this form of the condition is very rare, and it is unclear whether these individuals have a distinct form of the disease or whether they have intermediate or intermittent MSUD. Additionally, none of these individuals are treated only with thiamine, and they typically need other supplements in addition to dietary restrictions.

How common is Maple Syrup Urine Disease Type Ia?

The incidence of MSUD in the population is approximately 1 in 185,000 infants. MSUD type Ia, caused by mutations in the gene BCKDHA, is thought to account for approximately 45% of all diagnoses of MSUD. The incidence of MSUD type Ia is more common among individuals of Old Order Mennonite and Portuguese Gypsy descent.

How is Maple Syrup Urine Disease Type Ia treated?

MSUD is primarily controlled by diet, using foods low in protein. This often means severe restrictions on meat, fish, eggs, dairy foods, whole-grain flour, beans, and nuts. Additionally, individuals with MSUD are given prescription medical foods and a special liquid formula that supplies needed nutrients without extra proteins they cannot digest. These dietary restrictions should begin immediately upon diagnosis and must continue for the individual's entire life.

Careful management is the key to effective treatment. Protein levels should be closely monitored by a physician, and dietary adjustments should be made as needed. 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. Individuals with MSUD are particularly vulnerable during times of illness and should promptly consult a physician if they do not feel well. Affected individuals may need a special "sick-day diet" to avoid hospital stays. Individuals with mood, anxiety, or attention and hyperactivity disorders generally respond well to the standard medications for those conditions.

Liver transplant is an effective treatment and can often allow individuals with MSUD to have a normal diet. However, transplants cannot reverse any developmental disability or mental illness associated with the condition.

What is the prognosis for an individual with Maple Syrup Urine Disease Type Ia?

If untreated, MSUD can be fatal. With early, careful, and lifelong treatment and a low-protein diet, people with MSUD can live healthy lives into adulthood and show normal growth and mental development. Liver transplantation can reduce or eliminate the need for dietary management, but it cannot reverse any developmental delays or mood disorders. It is critical to recognize the disease as soon as symptoms appear in order to avoid brain damage and mental disability. Despite careful treatment, some people with the disease will experience periodic flare-ups, particularly during times of illness. These episodes may create learning problems or intellectual disability and can be life-threatening.

Other names for
maple syrup urine disease type Ia

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


  • Blackburn et al., 2017, Appl Clin Genet, 10:57-66, PMID: 28919799
  • Nellis et al., 2003, Mol Genet Metab, 80(1-2):189-95, PMID: 14567968
  • Puffenberger, 2003, Am J Med Genet C Semin Med Genet, 121C(1):18-31, PMID: 12888983
  • Quental et al., 2008, Mol Genet Metab, 94(2):148-56, PMID: 18378174
  • Rodríguez-Pombo et al., 2006, Hum Mutat, 27(7):715, PMID: 16786533
  • Strauss et al., 2020, http://www.ncbi.nlm.nih.gov/books/NBK1319/