Abstract:
:The congenital disorders of glycosylation (CDG) are inborn errors of metabolism with a great genetic heterogeneity. Most CDG are caused by defects in the N-glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue-restricted clinical symptoms in the various defects in dolichol-phosphate-mannose (DPM) synthesis remains unexplained. To deepen our understanding of the tissue-specific characteristics of defects in the DPM synthesis pathway, we investigated N-glycosylation and O-mannosylation in skeletal muscle of three DPM3-CDG patients presenting with muscle dystrophy and hypo-N-glycosylation of serum transferrin in only two of them. In the three patients, O-mannosylation of alpha-dystroglycan (αDG) was strongly reduced and western blot analysis of beta-dystroglycan (βDG) N-glycosylation revealed a consistent lack of one N-glycan in skeletal muscle. Recently, defective N-glycosylation of βDG has been reported in patients with mutations in guanosine-diphosphate-mannose pyrophosphorylase B (GMPPB). Thus, we suggest that aberrant O-glycosylation of αDG and N-glycosylation of βDG in skeletal muscle is indicative of a defect in the DPM synthesis pathway. Further studies should address to what extent hypo-N-glycosylation of βDG or other skeletal muscle proteins contribute to the phenotype of patients with defects in DPM synthesis. Our findings contribute to our understanding of the tissue-restricted phenotype of DPM3-CDG and other defects in the DPM synthesis pathway.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
van Tol W,Michelakakis H,Georgiadou E,van den Bergh P,Moraitou M,Papadimas GK,Papadopoulos C,Huijben K,Alsady M,Willemsen MA,Lefeber DJdoi
10.1002/jimd.12095subject
Has Abstractpub_date
2019-09-01 00:00:00pages
984-992issue
5eissn
0141-8955issn
1573-2665journal_volume
42pub_type
杂志文章abstract::Hurler-Scheie syndrome is caused by alpha-l-iduronidase deficiency. Enzyme replacement therapy (ERT) can improve physical capacity and reduces organomegaly. However, the effect on bradytrophic connective tissue is limited. As intravenously administered enzyme cannot cross the blood-brain barrier, the therapy of choice...
journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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abstract::Maple syrup urine disease (MSUD) is an autosomal recessive inherited disease due to a deficiency of any of the subunits, E1 alpha, E1 beta or E2, of the branched-chain alpha-ketoacid dehydrogenase complex (BCKDH). A large Mennonite kindred of MSUD has been studied in Pennsylvania, USA. In the present investigation, ge...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799628
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1024000202364
更新日期:2003-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
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abstract::Insulinaemia and glucagonaemia were measured in two cases of hypercholesterolaemia type II, before and after portacaval shunt. The results show an increase of both hormones although these variations are not concomitant with the decrease in cholesterolaemia. The data still do not explain the mechanism of the decrease. ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01801719
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journal_title:Journal of inherited metabolic disease
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doi:10.1023/a:1005369926784
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-014-9803-7
更新日期:2015-09-01 00:00:00
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-010-9161-z
更新日期:2011-02-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 临床试验,杂志文章
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更新日期:2001-12-01 00:00:00
abstract::Sandhoff disease is caused by the defective activity of the lysosomal enzyme beta-hexosaminidase, resulting in accumulation of the glycolipids, GA2 and GM2. Niemann-Pick A/B disease is caused by the defective activity of lysosomal acid sphingomyelinase resulting in sphingomyelin accumulation. Pulmonary complications h...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/b:boli.0000042958.22066.6c
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2010-02-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800371
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005513626542
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
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更新日期:2018-05-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799522
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF02312543
更新日期:1980-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005318308422
更新日期:1997-09-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-008-1052-1
更新日期:2008-12-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type:
doi:10.1007/s10545-014-9731-6
更新日期:2014-09-01 00:00:00