maple syrup urine disease type 1B
What is Maple Syrup Urine Disease Type 1B?
Maple syrup urine disease (MSUD) type 1B is an inherited metabolic disorder named for the characteristic maple syrup smell of the affected person’s urine. If carefully treated with a low-protein diet, people with MSUD can live fairly normal lives.
MSUD is caused by the lack of an enzyme needed to break down three amino acids: leucine, isoleucine, and valine, which are collectively known as the 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), these amino acids and their byproducts accumulate and cause damage to the body. MSUD type 1B is due to a defect in one of the four components of the BCKAD enzyme.
Maple syrup urine disease can be classified into four general types: classic, intermediate, intermittent, and thiamine-responsive. Classic MSUD is the most severe type. People 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 mental and physical disability.
The most common type, classic MSUD is characterized by little or no enzyme activity. Symptoms in people 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 smell. (Mediterranean populations unfamiliar with maple syrup describe the odor as similar to fenugreek.)
Within several days, the infant will show poor feeding, vomiting, and irritability, followed by lack of energy, weight loss, seizures, a tense arched posture, muscle tone which 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 and most will die within several months.
Upon any lapse of treatment, classic MSUD can cause brain damage. People with the disease are particularly prone to crisis during illness, infection, fasting, or after surgery.
People with intermediate MSUD have 3 to 8% of the normal amount of BCKAD enzyme activity. As a result, their bodies can tolerate higher amounts of the amino acid leucine. When ill, however, this tolerance drops.
Intermediate MSUD is similar to but less severe than the classic form. During periods of crisis, however, symptoms and risks are nearly identical.
With intermittent MSUD, BCKAD enzyme activity is often between 8 and 15% of normal. Symptoms of the disease may not appear until the first or second year of life. Symptoms often appear during illness, fasting, or periods of high protein consumption.
This form of the disease is rare, but in times of crisis its risks and symptoms are similar to the classic form.
Thiamine-responsive MSUD is distinct in that people with this form of the disease will respond to large doses of thiamine. One study found that people with thiamine-responsive MSUD have 30 to 40% the normal activity of the BCKAD enzyme. Many people with this form of the disease can tolerate some protein in their diet.
In times of crisis, the risks and symptoms of thiamine-responsive MSUD are similar to the classic form. The ability to treat the disease with thiamine, however, makes it easier to control than the other forms, whose treatment hinges largely on diet.
How common is Maple Syrup Urine Disease Type 1B?
Worldwide, MSUD type 1B is estimated to affect 1 in 185,000 infants. It is most common among the Old Order Mennonite population, where about 1 in 385 infants is affected by the disease. Among Mennonites of eastern Pennsylvania, the frequency has been reported as high as 1 in 176 infants. The disease is also more common among Ashkenazi Jews, with roughly 1 in 50,000 affected by MSUD type 1B.
How is Maple Syrup Urine Disease Type 1B treated?
MSUD type 1B is primarily controlled by diet, using foods low in protein. This often means severe restrictions on meat, fish, eggs, dairy foods, wholegrain flour, beans, and nuts. Often people with MSUD type 1B 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 person’s entire life.
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 a person with MSUD type 1B. He or she may need a special “sick day diet” to avoid hospital stays.
Those with thiamine-responsive MSUD may be prescribed thiamine supplements.
What is the prognosis for a person with Maple Syrup Urine Disease Type 1B?
With early, careful, and lifelong treatment, people with MSUD type 1B 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 people with the disease will experience periodic flare-ups, particularly during times of illness. These may create learning problems or mental disability and can be life-threatening.
If untreated, MSUD can be fatal.