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Maple syrup urine disease | ||||||||
In a few days, though, things start to change. At first, you were happy that the feeding cycle was longer than the typical four hours, but the baby just does not seem hungry. Likewise, the baby that once kicked imaginary soccer goals now lies quietly in her bassinet. And the odor that you first put down to that new baby smell has taken on the tang of maple syrup. Something is wrong.
First characterized in 1954 by John Menkes, the pediatrician who later described Menkes disease (see Modern Drug Discovery, Aug 2001, p 80), maple syrup urine disease (MSUD) is due to a disruption in the metabolism of the branched-chain amino acids (BCAAs)leucine, isoleucine, and valineand the resulting buildup of
![]() As indicated above, the early symptoms of the disease include lethargy and a loss of appetite within the first few days after birth as the infants go into ketoacidosis. Unrecognized and untreated, the disease leads to vomiting, seizures, coma, and sometimes death. Thus, it is critical that the disease be caught early by a simple blood test to determine the serum levels of the BCAAs and their respective Because the pathology of the disease is poorly understood, little has been accomplished in the development of preventive treatments. One way to limit A new treatment, however, may be forthcoming in the form of a compound isolated from sharks and rays, trimethylamine N-oxide (TMAO). A few of the MSUD mutations cause subunits of the BCKD to be misfolded, inhibiting complex formation and normal function. TMAO is a natural osmolyte and has been shown to facilitate the correct folding of a variety of disease-related proteins. David Chuang and his group at the University of Texas South western Medical Center (Dallas) recently applied TMAO to the problem of MSUD. They found that, in vitro, the compound returned some function to the BCKD complex. There is still a long road, however, between in vitro success and human treatment. Further reading
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