https://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&feed=atom&action=historyCanavan Disease - Revision history2024-03-29T12:13:51ZRevision history for this page on the wikiMediaWiki 1.31.16https://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38683&oldid=prevMahlich at 09:50, 5 September 20132013-09-05T09:50:39Z<p></p>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Canavan disease pathway KEGG.png|thumb|750px|'''<caption>'''Alanine, Aspartate and Glutamate Metabolism (source: [http://www.kegg.jp/kegg-bin/show_pathway?hsadd00250+443 KEGG]) highlighting disease associated enzymes of Canavan Disease.</caption>]]</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Canavan disease pathway KEGG.png|thumb|750px|'''<caption>'''Alanine, Aspartate and Glutamate Metabolism (source: [http://www.kegg.jp/kegg-bin/show_pathway?hsadd00250+443 KEGG]) highlighting disease associated enzymes of Canavan Disease.</caption>]]</div></td>
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<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
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<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease belongs to the group of leukodystrophies. The etymological origin are the greek words: λευκος ''leukos'' "white", δυς ''dys'' "bad, wrong" and τροφη ''trophae'' "feeding, growth". This is a genetic induced metabolic disorder, which affects the white matter of the nervous system. If the white matter is not properly grown, the myelin, which surrounds the nerve cells for protection, is degraded. This is especially true for Canavan Disease. The visible phenotypes are a result of a genetic defect that negatively affects the growth of the myelin sheath covering the nerve fibers. <del class="diffchange diffchange-inline">A</del> improperly build myelin sheath, results in a reduced ability to transmit the electric signal along the nerve fibers, eventually losing it completely and finally the degradation of whole nerve cells. <br></div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease belongs to the group of leukodystrophies. The etymological origin are the greek words: λευκος ''leukos'' "white", δυς ''dys'' "bad, wrong" and τροφη ''trophae'' "feeding, growth". This is a genetic induced metabolic disorder, which affects the white matter of the nervous system. If the white matter is not properly grown, the myelin, which surrounds the nerve cells for protection, is degraded. This is especially true for Canavan Disease. The visible phenotypes are a result of a genetic defect that negatively affects the growth of the myelin sheath covering the nerve fibers. <ins class="diffchange diffchange-inline">An</ins> improperly build myelin sheath, results in a reduced ability to transmit the electric signal along the nerve fibers, eventually losing it completely and finally the degradation of whole nerve cells. <br></div></td>
</tr>
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<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The cause for the malfunctioning myelin sheath growth is a genetic defect of the aspartoacylase (ASPA) gene. The product of the gene, the enzyme aspartoacylase is crucial in the degradation process of N-acetyl-L-aspartate (NAA) which is present at much higher levels than normal in patients suffering from Canavan Disease. Normally ASPA would degrade NAA into smaller fragments which are required prerequisites for the production of the myelin sheath (see '''<xr id="KEGG">Figure</xr>''' for an overview where APSA is located in the metabolic map). Therefore the missing / defective ASPA is reason for the defective build up process of myelin. The degradation of the nerve cells / white brain matter has the consequence that empty spaces are arising which are filled with brain fluid leading to even more degradation of nerve cells and signal transduction problems.</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The cause for the malfunctioning myelin sheath growth is a genetic defect of the aspartoacylase (ASPA) gene. The product of the gene, the enzyme aspartoacylase is crucial in the degradation process of N-acetyl-L-aspartate (NAA) which is present at much higher levels than normal in patients suffering from Canavan Disease. Normally ASPA would degrade NAA into smaller fragments which are required prerequisites for the production of the myelin sheath (see '''<xr id="KEGG">Figure</xr>''' for an overview where APSA is located in the metabolic map). Therefore the missing / defective ASPA is reason for the defective build up process of myelin. The degradation of the nerve cells / white brain matter has the consequence that empty spaces are arising which are filled with brain fluid leading to even more degradation of nerve cells and signal transduction problems.</div></td>
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<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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</table>Mahlichhttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38682&oldid=prevMahlich: /* Inheritance */2013-09-05T09:46:28Z<p><span dir="auto"><span class="autocomment">Inheritance</span></span></p>
<table class="diff diff-contentalign-left" data-mw="interface">
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<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">Revision as of 09:46, 5 September 2013</td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Inheritance ==</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Inheritance ==</div></td>
</tr>
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<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease is an autosomal recessive genetic defect of the ASPA (aspartoacyclase) gene on chromosome 17 (for the crystal structure of the ASPA protein see '''<xr id="ASPA">Figure</xr>'''). With this pattern of heritage a newborn of a couple where both parents are carriers of the defective genome has a 25% chance neither being born suffering from Canavan Disease nor being born a carrier. For some time children born of Ashkenazi Jewish ancestry had a higher prevalence of having Canavan Disease while in the last years this prevalence is sinking due to ongoing prenatal screening programs. Other ethnic groups where Canavan Disease has a higher penetrance are for example populations of Saudi Arabian ancestry. <br></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease is an autosomal recessive genetic defect of the ASPA (aspartoacyclase) gene on chromosome 17 (for the crystal structure of the ASPA protein see '''<xr id="ASPA">Figure</xr>'''). With this pattern of heritage a newborn of a couple where both parents are carriers of the defective genome has a 25% chance neither being born suffering from Canavan Disease nor being born a carrier. For some time children born of Ashkenazi Jewish ancestry had a higher prevalence of having Canavan Disease while in the last years this prevalence is sinking due to ongoing prenatal screening programs. Other ethnic groups where Canavan Disease has a higher penetrance are for example populations of Saudi Arabian ancestry. <br></div></td>
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<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>According to [http://ghr.nlm.nih.gov/condition/canavan-disease ''Genetics Home''] about one in 6400 to 13500 of the Ashkenazi Jewish are affected. No further information about prevalences in other populations was found. However the different populations have also different frequencies regarding the mutation they are based on. For further information see section [Canavan_Disease#Disease_Causing_Mutations ''Disease Causing Mutations''].</div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>According to [http://ghr.nlm.nih.gov/condition/canavan-disease ''Genetics Home''] about one in 6400 to 13500 of the Ashkenazi Jewish are affected. No further information about prevalences in other populations was found. However the different populations have also different frequencies regarding the mutation they are based on. For further information see section <ins class="diffchange diffchange-inline">[</ins>[Canavan_Disease#Disease_Causing_Mutations<ins class="diffchange diffchange-inline">|</ins> ''Disease Causing Mutations''<ins class="diffchange diffchange-inline">]</ins>].</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Phenotype ==</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Phenotype ==</div></td>
</tr>
</table>Mahlichhttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38681&oldid=prevMahlich: /* Inheritance */2013-09-05T09:45:51Z<p><span dir="auto"><span class="autocomment">Inheritance</span></span></p>
<table class="diff diff-contentalign-left" data-mw="interface">
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<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">Revision as of 09:45, 5 September 2013</td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Inheritance ==</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Inheritance ==</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease is an autosomal recessive genetic defect of the ASPA (aspartoacyclase) gene on chromosome 17 (for the crystal structure of the ASPA protein see '''<xr id="ASPA">Figure</xr>'''). With this pattern of heritage a newborn of a couple where both parents are carriers of the defective genome has a 25% chance neither being born suffering from Canavan Disease nor being born a carrier. For some time children born of Ashkenazi Jewish ancestry had a higher prevalence of having Canavan Disease while in the last years this prevalence is sinking due to ongoing prenatal screening programs. Other ethnic groups where Canavan Disease has a higher penetrance are for example populations of Saudi Arabian ancestry. <br></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease is an autosomal recessive genetic defect of the ASPA (aspartoacyclase) gene on chromosome 17 (for the crystal structure of the ASPA protein see '''<xr id="ASPA">Figure</xr>'''). With this pattern of heritage a newborn of a couple where both parents are carriers of the defective genome has a 25% chance neither being born suffering from Canavan Disease nor being born a carrier. For some time children born of Ashkenazi Jewish ancestry had a higher prevalence of having Canavan Disease while in the last years this prevalence is sinking due to ongoing prenatal screening programs. Other ethnic groups where Canavan Disease has a higher penetrance are for example populations of Saudi Arabian ancestry. <br></div></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>According to [http://ghr.nlm.nih.gov/condition/canavan-disease ''Genetics Home''] about one in 6400 to 13500 of the Ashkenazi Jewish are affected. No further information about prevalences in other populations was found. However the different populations have also different frequencies regarding the mutation they are based on. For further information see section [<del class="diffchange diffchange-inline">https://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php/</del>Canavan_Disease#Disease_Causing_Mutations ''Disease Causing Mutations''].</div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>According to [http://ghr.nlm.nih.gov/condition/canavan-disease ''Genetics Home''] about one in 6400 to 13500 of the Ashkenazi Jewish are affected. No further information about prevalences in other populations was found. However the different populations have also different frequencies regarding the mutation they are based on. For further information see section [Canavan_Disease#Disease_Causing_Mutations ''Disease Causing Mutations''].</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Phenotype ==</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Phenotype ==</div></td>
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</table>Mahlichhttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38488&oldid=prevBoehma at 14:43, 4 September 20132013-09-04T14:43:23Z<p></p>
<table class="diff diff-contentalign-left" data-mw="interface">
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<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">Revision as of 14:43, 4 September 2013</td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Canavan disease pathway KEGG.png|thumb|750px|'''<caption>'''Alanine, Aspartate and Glutamate Metabolism (source: [http://www.kegg.jp/kegg-bin/show_pathway?hsadd00250+443 KEGG]) highlighting disease associated enzymes of Canavan Disease.</caption>]]</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:Canavan disease pathway KEGG.png|thumb|750px|'''<caption>'''Alanine, Aspartate and Glutamate Metabolism (source: [http://www.kegg.jp/kegg-bin/show_pathway?hsadd00250+443 KEGG]) highlighting disease associated enzymes of Canavan Disease.</caption>]]</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease belongs to the group of leukodystrophies. The <del class="diffchange diffchange-inline">ethymological</del> origin are the greek words: λευκος ''leukos'' "white", δυς ''dys'' "bad, wrong" and τροφη ''trophae'' "feeding, growth". This is a genetic induced metabolic disorder, which affects the white matter of the nervous system. If the white matter is not properly grown, the myelin, which surrounds the nerve cells for protection, is degraded. This is especially true for Canavan Disease. The visible phenotypes are a result of a genetic defect that negatively affects the growth of the myelin sheath covering the nerve <del class="diffchange diffchange-inline">fibres</del>. A improperly build myelin sheath, results in a reduced ability to transmit the electric signal along the nerve <del class="diffchange diffchange-inline">fibres</del>, eventually losing it completely and finally the degradation of whole nerve cells. <br></div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease belongs to the group of leukodystrophies. The <ins class="diffchange diffchange-inline">etymological</ins> origin are the greek words: λευκος ''leukos'' "white", δυς ''dys'' "bad, wrong" and τροφη ''trophae'' "feeding, growth". This is a genetic induced metabolic disorder, which affects the white matter of the nervous system. If the white matter is not properly grown, the myelin, which surrounds the nerve cells for protection, is degraded. This is especially true for Canavan Disease. The visible phenotypes are a result of a genetic defect that negatively affects the growth of the myelin sheath covering the nerve <ins class="diffchange diffchange-inline">fibers</ins>. A improperly build myelin sheath, results in a reduced ability to transmit the electric signal along the nerve <ins class="diffchange diffchange-inline">fibers</ins>, eventually losing it completely and finally the degradation of whole nerve cells. <br></div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The cause for the malfunctioning myelin sheath growth is a genetic defect of the aspartoacylase (ASPA) gene. The product of the gene, the enzyme aspartoacylase is crucial in the degradation process of N-acetyl-L-aspartate (NAA) which is present at much higher levels than normal in patients suffering from Canavan Disease. Normally ASPA would degrade NAA into smaller fragments which are required prerequisites for the production of the myelin sheath (see '''<xr id="KEGG">Figure</xr>''' for an overview where APSA is located in the metabolic map). Therefore the missing / defective ASPA is reason for the defective build up process of myelin. The degradation of the nerve cells / white brain matter has the consequence that empty spaces are arising which are filled with brain fluid leading to even more degradation of nerve cells and signal transduction problems.</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The cause for the malfunctioning myelin sheath growth is a genetic defect of the aspartoacylase (ASPA) gene. The product of the gene, the enzyme aspartoacylase is crucial in the degradation process of N-acetyl-L-aspartate (NAA) which is present at much higher levels than normal in patients suffering from Canavan Disease. Normally ASPA would degrade NAA into smaller fragments which are required prerequisites for the production of the myelin sheath (see '''<xr id="KEGG">Figure</xr>''' for an overview where APSA is located in the metabolic map). Therefore the missing / defective ASPA is reason for the defective build up process of myelin. The degradation of the nerve cells / white brain matter has the consequence that empty spaces are arising which are filled with brain fluid leading to even more degradation of nerve cells and signal transduction problems.</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
</tr>
<tr>
<td colspan="2" class="diff-lineno">Line 70:</td>
<td colspan="2" class="diff-lineno">Line 70:</td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Neonatal / Infantile Treatment ====</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Neonatal / Infantile Treatment ====</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Since Canavan Disease also affects the metabolism there is need to control the nutrition and hydration. This includes specialized food to compensate missing metabolites and nutrients as well as different ways of feeding / providing nutrition to the child to prevent problems arising from swallowing difficulties and other physical disabilities. To improve those physical disabilities and muscle problems, it is recommended that children need physical therapy. Additionally there are <del class="diffchange diffchange-inline">antiepileptic</del> drugs against seizures and spastic <del class="diffchange diffchange-inline">behaviour</del>.</div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Since Canavan Disease also affects the metabolism there is need to control the nutrition and hydration. This includes specialized food to compensate missing metabolites and nutrients as well as different ways of feeding / providing nutrition to the child to prevent problems arising from swallowing difficulties and other physical disabilities. To improve those physical disabilities and muscle problems, it is recommended that children need physical therapy. Additionally there are <ins class="diffchange diffchange-inline">anti-epileptic</ins> drugs against seizures and spastic <ins class="diffchange diffchange-inline">behavior</ins>.</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Mild / Juvenile Treatment ====</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Mild / Juvenile Treatment ====</div></td>
</tr>
<tr>
<td colspan="2" class="diff-lineno">Line 82:</td>
<td colspan="2" class="diff-lineno">Line 82:</td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Gene Therapy ====</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Gene Therapy ====</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>There were several studies in the gene therapy, using viral and <del class="diffchange diffchange-inline">nonviral</del> vectors to transfer genes into the patients that were thought to improve the course of the disease. However none of the children showed an improvement and the disease showed a development similar to an untreated patient. </div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>There were several studies in the gene therapy, using viral and <ins class="diffchange diffchange-inline">non viral</ins> vectors to transfer genes into the patients that were thought to improve the course of the disease. However none of the children showed an improvement and the disease showed a development similar to an untreated patient. </div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Lithium Citrate as Pharmaceutical ====</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Lithium Citrate as Pharmaceutical ====</div></td>
</tr>
<tr>
<td colspan="2" class="diff-lineno">Line 150:</td>
<td colspan="2" class="diff-lineno">Line 150:</td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|-</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|-</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|| Deletion / duplication analysis</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|| Deletion / duplication analysis</div></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|colspan="2"| Large genomic deletions/<del class="diffchange diffchange-inline">duplictions</del> <br> comprising one or more exons</div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|colspan="2"| Large genomic deletions/<ins class="diffchange diffchange-inline">duplications</ins> <br> comprising one or more exons</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|| N/A</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|| N/A</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|| Unknown (<10%)</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|| Unknown (<10%)</div></td>
</tr>
</table>Boehmahttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38446&oldid=prevBoehma at 12:05, 4 September 20132013-09-04T12:05:09Z<p></p>
<table class="diff diff-contentalign-left" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en">
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">Revision as of 12:05, 4 September 2013</td>
</tr><tr>
<td colspan="2" class="diff-lineno">Line 1:</td>
<td colspan="2" class="diff-lineno">Line 1:</td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><figure id="ASPA"></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><figure id="ASPA"></div></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>[[Image:ASPA_CANAVAN_2O4H.png|thumb|450px|'''<caption>'''Crystal structure of aspartoacylase (2O4H - <del class="diffchange diffchange-inline">PDBfile</del>).</caption>]]</div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>[[Image:ASPA_CANAVAN_2O4H.png|thumb|450px|'''<caption>'''Crystal structure of aspartoacylase (2O4H - <ins class="diffchange diffchange-inline">PDB-file</ins>).</caption>]]</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>'''Canavan Disease''' ([http://apps.who.int/classifications/icd10/browse/2010/en#/E75.2 ICD-10 E75.2]) is an autosomal recessive disorder, in which a dysfunctional enzyme causes severe brain damage. It is also known under a variety of other names describing the chemical basis or phenotype of the disease. Examples are "Spongy Degeneration Of Central Nervous System", "Aspartoacylase (ASPA) Deficiency", or "Aminoacylase 2 (ACY2) Deficiency"[http://omim.org/entry/271900]. The trivial name, Canavan Disease, originates from the name of Myrtelle Canavan (1879 – 1953)[http://en.wikipedia.org/wiki/Myrtelle_Canavan], an American physician, who first described the disease in 1931. </div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>'''Canavan Disease''' ([http://apps.who.int/classifications/icd10/browse/2010/en#/E75.2 ICD-10 E75.2]) is an autosomal recessive disorder, in which a dysfunctional enzyme causes severe brain damage. It is also known under a variety of other names describing the chemical basis or phenotype of the disease. Examples are "Spongy Degeneration Of Central Nervous System", "Aspartoacylase (ASPA) Deficiency", or "Aminoacylase 2 (ACY2) Deficiency"[http://omim.org/entry/271900]. The trivial name, Canavan Disease, originates from the name of Myrtelle Canavan (1879 – 1953)[http://en.wikipedia.org/wiki/Myrtelle_Canavan], an American physician, who first described the disease in 1931. </div></td>
</tr>
</table>Boehmahttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38445&oldid=prevBoehma at 12:03, 4 September 20132013-09-04T12:03:05Z<p></p>
<a href="https://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=38445&oldid=36967">Show changes</a>Boehmahttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=36967&oldid=prevMahlich at 13:17, 29 August 20132013-08-29T13:17:53Z<p></p>
<table class="diff diff-contentalign-left" data-mw="interface">
<col class="diff-marker" />
<col class="diff-content" />
<col class="diff-marker" />
<col class="diff-content" />
<tr class="diff-title" lang="en">
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #222; text-align: center;">Revision as of 13:17, 29 August 2013</td>
</tr><tr>
<td colspan="2" class="diff-lineno">Line 2:</td>
<td colspan="2" class="diff-lineno">Line 2:</td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:ASPA_CANAVAN_2O4H.png|thumb|450px|'''<caption>'''Crystal structure of aspartoacylase (2O4H - PDBfile)</caption>]]</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:ASPA_CANAVAN_2O4H.png|thumb|450px|'''<caption>'''Crystal structure of aspartoacylase (2O4H - PDBfile)</caption>]]</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
</tr>
<tr>
<td class="diff-marker">−</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>'''Canavan Disease''' ([http://apps.who.int/classifications/icd10/browse/2010/en#/E75.2 ICD-10 E75.2]) is an autosomal recessive disorder, in which a dysfunctional enzyme causes severe brain damage. It is also known under a variety of other names describing the chemical basis or phenotype of the disease. Examples are "Spongy Degeneration Of Central Nervous System", "Aspartoacylase (ASPA) Deficiency", or "Aminoacylase 2 (ACY2) Deficiency"<del class="diffchange diffchange-inline">[</del>[http://omim.org/entry/271900<del class="diffchange diffchange-inline">]</del>]. The trivial name, Canavan Disease, originates from the name of Myrtelle Canavan (1879 – 1953)<del class="diffchange diffchange-inline">[</del>[http://en.wikipedia.org/wiki/Myrtelle_Canavan<del class="diffchange diffchange-inline">]</del>], an American physician, who first described the disease in 1931. </div></td>
<td class="diff-marker">+</td>
<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>'''Canavan Disease''' ([http://apps.who.int/classifications/icd10/browse/2010/en#/E75.2 ICD-10 E75.2]) is an autosomal recessive disorder, in which a dysfunctional enzyme causes severe brain damage. It is also known under a variety of other names describing the chemical basis or phenotype of the disease. Examples are "Spongy Degeneration Of Central Nervous System", "Aspartoacylase (ASPA) Deficiency", or "Aminoacylase 2 (ACY2) Deficiency"[http://omim.org/entry/271900]. The trivial name, Canavan Disease, originates from the name of Myrtelle Canavan (1879 – 1953)[http://en.wikipedia.org/wiki/Myrtelle_Canavan], an American physician, who first described the disease in 1931. </div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>There is no cure and almost all patients die within the first decade of their life. The mild / juvenile type is less severe. The treatment is based on the symptoms and is supportive.</div></td>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>There is no cure and almost all patients die within the first decade of their life. The mild / juvenile type is less severe. The treatment is based on the symptoms and is supportive.</div></td>
</tr>
<tr>
<td class="diff-marker"> </td>
<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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</table>Mahlichhttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=36960&oldid=prevMahlich: /* Disease Causing Mutations */2013-08-29T13:10:13Z<p><span dir="auto"><span class="autocomment">Disease Causing Mutations</span></span></p>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*[[ASPA#Protein Sequence|Reference sequence (protein) of ASPA]]</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>===== Disease Causing Mutations =====</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>===== Disease Causing Mutations =====</div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The disease causing mutations can be found in <del class="diffchange diffchange-inline">the</del> <del class="diffchange diffchange-inline">image</del> below. Also very interesting is the frequency across the different populations.</div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The disease causing mutations can be found in <ins class="diffchange diffchange-inline">'''<xr</ins> <ins class="diffchange diffchange-inline">id="DisCausMut">Table</xr>''' and '''<xr id="AllelicVar">Table</xr>'''</ins> below. Also very interesting is the frequency across the different populations.</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>{| border="1" cellpadding="5" cellspacing="0" align="center"</div></td>
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</table>Mahlichhttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=36959&oldid=prevMahlich: /* Aspartoacylase (ASPA) */2013-08-29T13:07:53Z<p><span dir="auto"><span class="autocomment">Aspartoacylase (ASPA)</span></span></p>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Summary ====</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Summary ====</div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Aspartoacylase is the enzyme that hydrolyses N-acetyl-L-aspartate into acetate and L-aspartate, which are essential for the build-up process of the myelin sheath. Crystallized ASPA exists as a homodimer however it is assumed that the in-vivo form only works as a monomer. The active site of ASPA contains a zinc atom which acts catalytic in the hydrolyzation process and is only accessible through a channel like surface fold of the protein. This channel like structure serves two purposes. On the one hand it hinders polypeptides to enter and bind at the active site, therefore ASPA does not function as protease. On the other hand and more importantly it is assumed, that the positive electrostatic potential that is present on the channel serves as a form of transport mechanism to properly carry the negatively charged substrate (NAA) to the hydrolyzing site. Furthermore, the binding pocket is highly specific to N-acetyl-L-aspartate with a far lower hydrolyzing activity towards other N-acetyl-amino complexes like N-acetylglutamate.</div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Aspartoacylase is the enzyme that hydrolyses N-acetyl-L-aspartate into acetate and L-aspartate, which are essential for the build-up process of the myelin sheath<ins class="diffchange diffchange-inline"> (chemical reaction displayed in '''<xr id="AspaKegg">Figure</xr>''')</ins>. Crystallized ASPA exists as a homodimer however it is assumed that the in-vivo form only works as a monomer. The active site of ASPA contains a zinc atom which acts catalytic in the hydrolyzation process and is only accessible through a channel like surface fold of the protein. This channel like structure serves two purposes. On the one hand it hinders polypeptides to enter and bind at the active site, therefore ASPA does not function as protease. On the other hand and more importantly it is assumed, that the positive electrostatic potential that is present on the channel serves as a form of transport mechanism to properly carry the negatively charged substrate (NAA) to the hydrolyzing site. Furthermore, the binding pocket is highly specific to N-acetyl-L-aspartate with a far lower hydrolyzing activity towards other N-acetyl-amino complexes like N-acetylglutamate.</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>==== Gene, Mutations ====</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The ASPA gene sits on chromosome 17 on the p-arm (upper part, short arm) band 1 subband 3 subsubband 2 (short 17p13.2).</div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The ASPA gene sits on chromosome 17 on the p-arm (upper part, short arm) band 1 subband 3 subsubband 2 (short 17p13.2<ins class="diffchange diffchange-inline">) (see '''<xr id="Location">Figure</xr>'''</ins>).</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><figure id="Location"></div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div><figure id="Location"></div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:ASPA gene location.png|thumb|centre|750px|'''<caption>'''Chromosome 17 with highlighted position of ASPA-gene (source: [http://www.genecards.org/cgi-bin/carddisp.pl?gene=ASPA Genecards])</caption>]]</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>[[Image:ASPA gene location.png|thumb|centre|750px|'''<caption>'''Chromosome 17 with highlighted position of ASPA-gene (source: [http://www.genecards.org/cgi-bin/carddisp.pl?gene=ASPA Genecards])</caption>]]</div></td>
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</table>Mahlichhttps://i12r-studfilesrv.informatik.tu-muenchen.de/wiki/index.php?title=Canavan_Disease&diff=36958&oldid=prevMahlich: /* Disease mechanism */2013-08-29T13:05:54Z<p><span dir="auto"><span class="autocomment">Disease mechanism</span></span></p>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div></figure></div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease belongs to the group of leukodystrophies. This comes from greek: λευκος ''leukos'' "white", δυς ''dys'' "bad, wrong", τροφη ''trophae'' "feeding, growth". This is a genetic induced metabolic disorder, which affects the white matter of the nervous system. If the white matter is not properly grown, the myelin, which surrounds the nerve cells for protection, is degraded. This is especially true for the Canavan Disease. The visible phenotypes are a result of a genetic defective that negatively affects the growth of the myelin sheath covering the nerve fibres. A improperly build myelin sheath, results in a reduced ability to transmitting the electric signal along the nerve fibres, eventually losing it completely and finally the degradation of whole nerve cells. <br></div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Canavan Disease belongs to the group of leukodystrophies. This comes from greek: λευκος ''leukos'' "white", δυς ''dys'' "bad, wrong", τροφη ''trophae'' "feeding, growth". This is a genetic induced metabolic disorder, which affects the white matter of the nervous system. If the white matter is not properly grown, the myelin, which surrounds the nerve cells for protection, is degraded. This is especially true for the Canavan Disease. The visible phenotypes are a result of a genetic defective that negatively affects the growth of the myelin sheath covering the nerve fibres. A improperly build myelin sheath, results in a reduced ability to transmitting the electric signal along the nerve fibres, eventually losing it completely and finally the degradation of whole nerve cells. <br></div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The cause for the malfunctioning myelin sheath growth is a genetic defect of the aspartoacylase (ASPA) gene. The product of the gene, the enzyme aspartoacylase is crucial in the degradation process of N-acetyl-L-aspartate (NAA) which is present at much higher levels<del class="diffchange diffchange-inline"> </del> than normal in patients suffering from Canavan Disease. Normally ASPA would degrade NAA into smaller fragments which are required prerequisites for the production of the myelin sheath. Therefore the missing / defective ASPA is reason for the defective generation of myelin. The degradation of the nerve cells / white brain matter has the consequence that empty spaces are arising which are filled with brain fluid leading to even more degradation of nerve cells and signal transduction problems.</div></td>
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<td style="color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The cause for the malfunctioning myelin sheath growth is a genetic defect of the aspartoacylase (ASPA) gene. The product of the gene, the enzyme aspartoacylase is crucial in the degradation process of N-acetyl-L-aspartate (NAA) which is present at much higher levels than normal in patients suffering from Canavan Disease. Normally ASPA would degrade NAA into smaller fragments which are required prerequisites for the production of the myelin sheath<ins class="diffchange diffchange-inline"> (see '''<xr id="KEGG">Figure</xr>''' for an overview where APSA is located in the metabolic map)</ins>. Therefore the missing / defective ASPA is reason for the defective generation of myelin. The degradation of the nerve cells / white brain matter has the consequence that empty spaces are arising which are filled with brain fluid leading to even more degradation of nerve cells and signal transduction problems.</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Diagnosis ==</div></td>
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<td style="background-color: #f8f9fa; color: #222; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Diagnosis ==</div></td>
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