Maple Syrup Urine Disease

Understanding this metabolic disorder

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Maple syrup urine disease (MSUD) is a genetic disorder that causes brain damage and progressive nervous system degeneration. The genetic defect that produces MSUD results in a defect in the enzyme called branched-chain alpha-keto acid dehydrogenase, (BCKD), which is necessary for the breakdown of the amino acids leucine, isoleucine, and valine. Without the BCKD enzyme, these amino acids build up to toxic levels in the body.

MSUD gets its name from the fact that, at times when blood amino acid levels are high, the urine takes on a distinctive sweet odor.

Maple syrup urine disease occurs in about 1 per 180,000 live births and affects both males and females. MSUD affects people of all ethnic backgrounds, but higher rates of the disorder occur in populations in which there is a lot of intermarriage, such as the Mennonite (Amish) community in Pennsylvania (U.S.).

Symptoms

There are several types of maple syrup urine disease. The most common (classic) form typically will produce symptoms in newborn infants aged 4-7 days. These symptoms may include:

  • Poor feeding
  • Vomiting
  • Poor weight gain
  • Increasing lethargy (difficult to wake up)
  • Characteristic burned sugar smell to urine
  • Changes in muscle tone, muscle spasms, and seizures

If left untreated, these infants will die with the first months of life.

Individuals with intermittent MSUD, the second most common form of the disorder, develop normally but when ill show the signs of classic MSUD.

Intermediate MSUD is a more rare form. Individuals with this type have 3-30% of the normal level of BCKD enzyme, so symptoms may begin at any age.

In thiamine-responsive MSUD, individuals show some improvement when given thiamine supplements.

A very rare form of the disorder is E3-deficient MSUD, in which individuals have additional deficient metabolic enzymes.

Diagnosis

If maple syrup urine disease is suspected based on the physical symptoms, especially the characteristic urine odor, a blood test for amino acids can be done. If alloisoleucine is detected, the diagnosis is confirmed. Routine screening of newborns for MSUD is done in several states within the U.S.

Treatment

The main treatment for maple syrup urine disease is restriction of dietary forms of the three amino acids leucine, isoleucine, and valine. These dietary restrictions must be lifelong. There are several commercial formulas and foods for individuals with MSUD.

One concern for treatment of MSUD is that when an affected individual is sick, injured, or has surgery, the disorder is exacerbated. Most individuals will require hospitalization during these times for medical management to prevent serious complications.

Fortunately, with adherence to the dietary restrictions and regular medical checkups individuals with maple syrup urine disease can live long and relatively healthy lives.

Sources:

Bodamer, O. A. (2003). Maple syrup urine disease. eMedicine, accessed at http://www.emedicine.com/ped/topic1368.htm

Morton DH, Strauss KA, Robinson DL, et al. Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics 2002; 109:999.

Edited by Richard N. Fogoros, MD

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