| Interrupting the mechanisms of brain injury in a model of maple syrup urine disease encephalopathy. | |
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MedLine Citation:
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PMID: 21541722 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Maple syrup urine disease (MSUD) was first recognized as an inherited lethal encephalopathy beginning in the first week of life and associated with an unusual odor in the urine of affected children. It was later confirmed as a deficiency of branched-chain keto acid dehydrogenase (BCKDH), which is the second step in branched-chain amino acid (BCAA) breakdown. MSUD is characterized by BCAA and branched-chain keto acid (BCKA) accumulation. BCAAs are essential amino acids and powerful metabolic signals with severe consequences of both deprivation and accumulation. Treatment requires life-long dietary restriction and monitoring of BCAAs. However, despite excellent compliance, children commonly suffer metabolic decompensation during intercurrent illness resulting in life-threatening cerebral edema and dysmyelination. The mechanisms underlying brain injury have been poorly understood. Recent studies using newly developed mouse models of both classic and intermediate MSUD have yielded insight into the consequences of rapid BCAA accumulation. Additionally, these models have been used to test preliminary treatments aimed at competing with blood-brain barrier transport of BCAA using norleucine. Assessment of biochemical changes with and without treatment suggests different roles for BCAA and BCKA in the mechanism of brain injury. |
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Authors:
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William J Zinnanti; Jelena Lazovic |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-4 |
Journal Detail:
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Title: Journal of inherited metabolic disease Volume: - ISSN: 1573-2665 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7910918 Medline TA: J Inherit Metab Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Room H3160, Stanford, CA, 94305, USA, zinnanti@stanford.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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