title: Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.
abstract: 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.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Li
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Gong
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.forename: De-Min
authors.initials: DM
authors.lastname: Yu
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Gu
authors.forename: Xiang-Wei
authors.initials: XW
authors.lastname: Liao
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Zhang
authors.forename: Xi-Qi
authors.initials: XQ
authors.lastname: Hu
authors.forename: Yue
authors.initials: Y
authors.lastname: Han
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Kong
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency; D000293:Adolescent; D002478:Cells, Cultured; D005227:Fatty Acids / Q000096:biosynthesis; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D015870:Gene Expression; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis; D008297:Male; D009154:Mutation
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D006004:Glycogen Debranching Enzyme System; D042964:Acyl-CoA Dehydrogenase; C020569:4 alpha-glucanotransferase; C030563:amylo-1,6-glucosidase