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Inherent lipid metabolic dysfunction in glycogen storage disease IIIa
•We report a new AGL mutation in a family severely affected by GSD III.•Glycogen storage diseases may give rise to a pathological acylcarnitine profile.•AGL mutation lead to an upregulation of genes encoding chemokines.•AGL mutation may affect PPAR and lipid/fatty acid biosynthesis signaling pathway...
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Published in: | Biochemical and biophysical research communications 2014-12, Vol.455 (1-2), p.90-97 |
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creator | Li, Xin-Hua Gong, Qi-Ming Ling, Yun Huang, Chong Yu, De-Min Gu, Lei-Lei Liao, Xiang-Wei Zhang, Dong-Hua Hu, Xi-Qi Han, Yue Kong, Xiao-Fei Zhang, Xin-Xin |
description | •We report a new AGL mutation in a family severely affected by GSD III.•Glycogen storage diseases may give rise to a pathological acylcarnitine profile.•AGL mutation lead to an upregulation of genes encoding chemokines.•AGL mutation may affect PPAR and lipid/fatty acid biosynthesis signaling pathway.
We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C>T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa. |
doi_str_mv | 10.1016/j.bbrc.2014.10.096 |
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We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C>T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2014.10.096</identifier><identifier>PMID: 25451272</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acyl-CoA Dehydrogenase - deficiency ; Adolescent ; AGL ; Cells, Cultured ; Fatty Acids - biosynthesis ; Fatty Acids, Unsaturated - biosynthesis ; Gene Expression ; Glycogen debranching enzyme ; Glycogen Debranching Enzyme System - genetics ; Glycogen Storage Disease Type III - diagnosis ; Glycogen Storage Disease Type III - genetics ; Glycogen Storage Disease Type III - metabolism ; Glycogen storage disease type IIIa ; Humans ; Lipid Metabolism, Inborn Errors - diagnosis ; Male ; MCAD ; Mutation</subject><ispartof>Biochemical and biophysical research communications, 2014-12, Vol.455 (1-2), p.90-97</ispartof><rights>2014 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-f96ce2da830ab1047e38edc33624e89d34ba442d25e93e8c9b42f7cb32a1aaab3</citedby><cites>FETCH-LOGICAL-c356t-f96ce2da830ab1047e38edc33624e89d34ba442d25e93e8c9b42f7cb32a1aaab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25451272$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Xin-Hua</creatorcontrib><creatorcontrib>Gong, Qi-Ming</creatorcontrib><creatorcontrib>Ling, Yun</creatorcontrib><creatorcontrib>Huang, Chong</creatorcontrib><creatorcontrib>Yu, De-Min</creatorcontrib><creatorcontrib>Gu, Lei-Lei</creatorcontrib><creatorcontrib>Liao, Xiang-Wei</creatorcontrib><creatorcontrib>Zhang, Dong-Hua</creatorcontrib><creatorcontrib>Hu, Xi-Qi</creatorcontrib><creatorcontrib>Han, Yue</creatorcontrib><creatorcontrib>Kong, Xiao-Fei</creatorcontrib><creatorcontrib>Zhang, Xin-Xin</creatorcontrib><title>Inherent lipid metabolic dysfunction in glycogen storage disease IIIa</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>•We report a new AGL mutation in a family severely affected by GSD III.•Glycogen storage diseases may give rise to a pathological acylcarnitine profile.•AGL mutation lead to an upregulation of genes encoding chemokines.•AGL mutation may affect PPAR and lipid/fatty acid biosynthesis signaling pathway.
We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C>T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.</description><subject>Acyl-CoA Dehydrogenase - deficiency</subject><subject>Adolescent</subject><subject>AGL</subject><subject>Cells, Cultured</subject><subject>Fatty Acids - biosynthesis</subject><subject>Fatty Acids, Unsaturated - biosynthesis</subject><subject>Gene Expression</subject><subject>Glycogen debranching enzyme</subject><subject>Glycogen Debranching Enzyme System - genetics</subject><subject>Glycogen Storage Disease Type III - diagnosis</subject><subject>Glycogen Storage Disease Type III - genetics</subject><subject>Glycogen Storage Disease Type III - metabolism</subject><subject>Glycogen storage disease type IIIa</subject><subject>Humans</subject><subject>Lipid Metabolism, Inborn Errors - diagnosis</subject><subject>Male</subject><subject>MCAD</subject><subject>Mutation</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp9kMtKw0AUhgdRbK2-gAvJ0k3q3DLJgBuRqoGCGwV3w1xO6pRc6kwi9O1NaHXp6sDh-3_O-RC6JnhJMBF326UxwS4pJnxcLLEUJ2hOsMQpJZifojnGWKRUko8ZuohxizEhXMhzNKMZzwjN6RytyvYTArR9Uvudd0kDvTZd7W3i9rEaWtv7rk18m2zqve020Cax74LeQOJ8BB0hKctSX6KzStcRro5zgd6fVm-PL-n69bl8fFinlmWiTyspLFCnC4a1GU_MgRXgLGOCciikY9xozqmjGUgGhZWG0yq3hlFNtNaGLdDtoXcXuq8BYq8aHy3UtW6hG6IiIqMsF5nMR5QeUBu6GANUahd8o8NeEawmfWqrJn1q0jftRn1j6ObYP5gG3F_k19cI3B8AGL_89hBUtB5aC84HsL1ynf-v_weRyYEw</recordid><startdate>20141205</startdate><enddate>20141205</enddate><creator>Li, Xin-Hua</creator><creator>Gong, Qi-Ming</creator><creator>Ling, Yun</creator><creator>Huang, Chong</creator><creator>Yu, De-Min</creator><creator>Gu, Lei-Lei</creator><creator>Liao, Xiang-Wei</creator><creator>Zhang, Dong-Hua</creator><creator>Hu, Xi-Qi</creator><creator>Han, Yue</creator><creator>Kong, Xiao-Fei</creator><creator>Zhang, Xin-Xin</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20141205</creationdate><title>Inherent lipid metabolic dysfunction in glycogen storage disease IIIa</title><author>Li, Xin-Hua ; Gong, Qi-Ming ; Ling, Yun ; Huang, Chong ; Yu, De-Min ; Gu, Lei-Lei ; Liao, Xiang-Wei ; Zhang, Dong-Hua ; Hu, Xi-Qi ; Han, Yue ; Kong, Xiao-Fei ; Zhang, Xin-Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-f96ce2da830ab1047e38edc33624e89d34ba442d25e93e8c9b42f7cb32a1aaab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acyl-CoA Dehydrogenase - deficiency</topic><topic>Adolescent</topic><topic>AGL</topic><topic>Cells, Cultured</topic><topic>Fatty Acids - biosynthesis</topic><topic>Fatty Acids, Unsaturated - biosynthesis</topic><topic>Gene Expression</topic><topic>Glycogen debranching enzyme</topic><topic>Glycogen Debranching Enzyme System - genetics</topic><topic>Glycogen Storage Disease Type III - diagnosis</topic><topic>Glycogen Storage Disease Type III - genetics</topic><topic>Glycogen Storage Disease Type III - metabolism</topic><topic>Glycogen storage disease type IIIa</topic><topic>Humans</topic><topic>Lipid Metabolism, Inborn Errors - diagnosis</topic><topic>Male</topic><topic>MCAD</topic><topic>Mutation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Xin-Hua</creatorcontrib><creatorcontrib>Gong, Qi-Ming</creatorcontrib><creatorcontrib>Ling, Yun</creatorcontrib><creatorcontrib>Huang, Chong</creatorcontrib><creatorcontrib>Yu, De-Min</creatorcontrib><creatorcontrib>Gu, Lei-Lei</creatorcontrib><creatorcontrib>Liao, Xiang-Wei</creatorcontrib><creatorcontrib>Zhang, Dong-Hua</creatorcontrib><creatorcontrib>Hu, Xi-Qi</creatorcontrib><creatorcontrib>Han, Yue</creatorcontrib><creatorcontrib>Kong, Xiao-Fei</creatorcontrib><creatorcontrib>Zhang, Xin-Xin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Xin-Hua</au><au>Gong, Qi-Ming</au><au>Ling, Yun</au><au>Huang, Chong</au><au>Yu, De-Min</au><au>Gu, Lei-Lei</au><au>Liao, Xiang-Wei</au><au>Zhang, Dong-Hua</au><au>Hu, Xi-Qi</au><au>Han, Yue</au><au>Kong, Xiao-Fei</au><au>Zhang, Xin-Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inherent lipid metabolic dysfunction in glycogen storage disease IIIa</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2014-12-05</date><risdate>2014</risdate><volume>455</volume><issue>1-2</issue><spage>90</spage><epage>97</epage><pages>90-97</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>•We report a new AGL mutation in a family severely affected by GSD III.•Glycogen storage diseases may give rise to a pathological acylcarnitine profile.•AGL mutation lead to an upregulation of genes encoding chemokines.•AGL mutation may affect PPAR and lipid/fatty acid biosynthesis signaling pathway.
We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C>T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25451272</pmid><doi>10.1016/j.bbrc.2014.10.096</doi><tpages>8</tpages></addata></record> |
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subjects | Acyl-CoA Dehydrogenase - deficiency Adolescent AGL Cells, Cultured Fatty Acids - biosynthesis Fatty Acids, Unsaturated - biosynthesis Gene Expression Glycogen debranching enzyme Glycogen Debranching Enzyme System - genetics Glycogen Storage Disease Type III - diagnosis Glycogen Storage Disease Type III - genetics Glycogen Storage Disease Type III - metabolism Glycogen storage disease type IIIa Humans Lipid Metabolism, Inborn Errors - diagnosis Male MCAD Mutation |
title | Inherent lipid metabolic dysfunction in glycogen storage disease IIIa |
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