What is maple syrup urine disease (MSUD)?

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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Icon Health. Maple Syrup Urine Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004.

Jorde, Lynn B., et al. Medical Genetics. 4th ed. St. Louis, Mo.: Mosby, 2009.

Mescka, Caroline P., et al. "Protein and Lipid Damage in Maple Syrup Urine Disease Patients: l-Carnitine Effect." International Journal of Developmental Neuroscience 31, no. 1 (February, 2013): 21–24.

Pritchard, Dorian J., and Bruce R. Korf. Medical Genetics at a Glance. 2d ed. Malden, Mass.: Blackwell Science, 2008.

Scaini, Giselli, et al. "DNA Damage in an Animal Model of Maple Syrup Urine Disease." Molecular Genetics and Metabolism 106, no. 2 (June, 2012): 169–174.

VeriMed Healthcare Network. "Maple Syrup Urine Disease." Medline Plus, May 15, 2011.