Maple syrup urine disease (MSUD)
Maple syrup urine disease (MSUD) is a rare genetic disorder caused by the deficiency or inactivity of a specific enzyme responsible for metabolizing branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine. This autosomal recessive condition leads to the accumulation of these amino acids and their toxic byproducts in the blood, particularly affecting brain function. Symptoms commonly emerge within the first few days of life and include poor weight gain, irritability, lethargy, a high-pitched cry, and a distinctive maple-syrup odor in the urine. If left untreated, MSUD can result in severe neurological issues, intellectual and developmental disabilities, and may be fatal.
The classic form of MSUD shows little enzyme activity, while variant forms may present milder symptoms due to partial enzyme function. Treatment involves a lifelong special diet that restricts the intake of the problematic amino acids to maintain metabolic control. Newborn screening for MSUD is crucial for early diagnosis and management, as timely intervention can significantly improve outcomes. The disease is more prevalent in certain populations, such as Mennonites, highlighting the importance of genetic awareness and carrier testing in affected communities.
Maple syrup urine disease (MSUD)
ALSO KNOWN AS: Branched-chain ketoaciduria
ANATOMY OR SYSTEM AFFECTED: Nervous system
DEFINITION: A recessive autosomal genetic disease resulting in the absence, partial activity, or inactivity of a multisubunit enzyme that is responsible for metabolizing the branched-chain amino acids leucine, isoleucine, and valine.
Causes and Symptoms
As a result of deficient branched-chain alpha-ketoacid dehydrogenase (BCKD), the essential branched chain amino acids leucine, isoleucine, and valine are not metabolized in patients with maple syrup urine disease (MSUD). The branched-chain amino acids and their ketoacid products accumulate in the blood and interfere with brain function. High levels of leucine are especially toxic. The classic form of the disease results in little (less than 2 percent) or no BCKD activity. Symptoms develop within three to seven days after birth and include poor weight gain, a high-pitched cry, irritability, lethargy, and a characteristic maple-syrup smell to the urine. If the disease is untreated, then intellectual and developmental disabilities, various neurological symptoms such as seizures, and even death can result.
Variant forms of the disease, in which there is some (3 to 12 percent) BCKD activity, result in milder symptoms. A rare variant form of the disease called thiamine-responsive MSUD responds to high doses of thiamine.
Treatment and Therapy
The treatment of severe MSUD, which should begin immediately after diagnosis, involves a special diet with controlled amounts of isoleucine, leucine, and valine to ensure metabolic control. Enfamil, a special dietary formula, provides leucine but may have to be supplemented with isoleucine and valine to provide adequate intake of all three amino acids and permit normal growth and development.
Treatment of the milder forms of MSUD also involves management through diet therapy. Diet therapy should be continued throughout life, and the levels of the branched-chain amino acids should be monitored often.
Perspective and Prospects
MSUD was first described in 1954. The name derives from the sweet, maple-syrup smell of the patient’s urine. Because MSUD is caused by a recessive gene, there is a one in four chance that two heterozygous carriers will have an affected child. MSUD affects about 1 in 185,000 newborns in the United States, but in some populations, such as Mennonites, it may be as high as 1 in 176.
Some hospitals test for the disease in their newborn screening programs. Testing should be done within the first twenty-four hours after birth, since early diagnosis is essential. Some of the milder variant forms are missed in the screening programs. The detection of alloisoleucine is diagnostic for MSUD but may not appear until the sixth day of life. Carrier testing is available for the Mennonite variant of the disease.
Bibliography
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"Maple Syrup Urine Disease." Medline Plus. National Institutes of Health, 1 July 2017, medlineplus.gov/genetics/condition/maple-syrup-urine-disease/. Accessed 1 Apr. 2024.
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