![maple syrup urine disease maple syrup urine disease](https://image.slidesharecdn.com/10-pangan-maplesyrupdisease-120924101253-phpapp01/95/10-pangan-maple-syrup-disease-8-728.jpg)
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 -keto acids. Unrecognized and untreated, the disease leads to vomiting, seizures, coma, and sometimes death. MSUD has been divided into six severity classes (Ia, Ib, II, III, IV, and V), which largely depend on which BCKD subunit has been mutated and the identity of the mutation.Īs 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. These genes encode for some of the proteins involved in the mitochondrial multienzyme complex branched-chain -ketoacid dehydrogenase (BCKD).
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The disease is inherited as an autosomal recessive disorder, but where this would normally imply that it is caused by the mutation of a single gene, MSUD can arise from mutations in several genes. The disease has an incidence in the United States of ~1/200,000. A buildup of -ketoacids during amino acid metabolism can be dangerous to a newborn infant. In fact, the isoleucyl ketoacid gives the urine its distinctive odor and the disease its name.īranched-chain amino acids. Something is wrong.įirst 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 -ketoacids. And the odor that you first put down to that new baby smell has taken on the tang of maple syrup.
![maple syrup urine disease maple syrup urine disease](https://image.slidesharecdn.com/maplesyrupurinedisease-110307062457-phpapp01/95/maple-syrup-urine-disease-msud-and-homocystinuria-21-728.jpg)
Likewise, the baby that once kicked imaginary soccer goals now lies quietly in her bassinet. At first, you were happy that the feeding cycle was longer than the typical four hours, but the baby just does not seem hungry. In a few days, though, things start to change. Its a girl. You quickly scan to see that the baby has all the requisite fingers and toes, and look to see whose nose hers looks like. These cows have many of the same disease features as seen in human patients, and our lab has acquired these animals to help further describe the disease as well as develop treatments for MSUD.∼ongratulations, says the nurse as he hands you the wriggling bundle. Cow model of MSUDĪ cow model of MSUD was first reported in Indiana. The Gray-Edwards lab is working closely with the Clinic for Special Children in Strasburg, Pennsylvania on this project. Ultimately, the quality of life of MSUD patients remains low and our goal in this lab is to develop a gene therapy that can help treat this devastating disease. Liver transplantation is a potential therapeutic strategy for MSUD but has major disadvantages, such as shortage of available organs, high inherent risks, and it does not alleviate behavioral/cognitive deficits. This scenario can potentially be prevented by careful dietary regulation consisting of BCAA-free diet, but it will not fully prevent MSUD crises (cerebral edema) nor development of behavioral and cognitive abnormalities like low IQ and psychiatric disorders. If not diagnosed immediately at birth, children will develop highly fatal cerebral edema (brain swelling) and subsequent coma in just a few days. Individuals with MSUD have poor feeding behaviors, lethargy, irritability, central respiratory failure, abnormal skeletal muscle function and neurological and cognitive abnormalities. Due to mutations in one of these genes results in a dysfunctional protein that can no longer break down these BCAA’s and thus causes toxic accumulation in cells throughout the body. This devastating disease is caused by a mutation in one of three genes, BCKDHA, BCKDHB and DBT, that forms a protein complex that breaks down large amino acids, branched-chain amino acids (BCAA’s) essential for life. Maple Syrup Urine Disease (MSUD) is a recessive metabolism disorder that causessevere neurological symptoms and causes fatal swelling of the brain in infants.