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maple syrup urine disease type Ia

What is Maple Syrup Urine Disease Type Ia?

Maple syrup urine disease (MSUD) type Ia is an inherited metabolic disorder named for the characteristic maple syrup smell of the affected person’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 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) complex, these amino acids and their byproducts accumulate and cause damage to the body. MSUD type Ia is due to a defect in one of the components of the BCKAD complex.

MSUD 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 intellectual and physical disability.

Classic Type

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. 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.

Intermediate Type

People with intermediate MSUD have some BCKAD enzyme activity. Thus, intermediate MSUD is similar to, but less severe than, the classic form. 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, not absent. Onset of the disease may not be until the first or second year of life. Symptoms are also 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 people 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 definitive.

How common is Maple Syrup Urine Disease Type Ia?

Worldwide, MSUD is estimated to affect 1 in 185,000 infants. MSUD type Ia is thought to account for approximately 30-40% of all diagnoses of maple syrup urine disease. Type Ia 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 Portuguese Gypsies, where it is estimated to affect 1 in 20,000 infants.

How is Maple Syrup Urine Disease Type Ia treated?

MSUD type Ia 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 Ia 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.

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 a person with MSUD type Ia. 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 utilized, therefore making it difficult to determine the true impact of a thiamine-only treatment plan.

What is the prognosis for a person 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 type Ia 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 intellectual 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.