scholarly journals An Unexplained Congenital Disorder of Glycosylation-II in a Child with Neurohepatic Involvement, Hypercholesterolemia and Hypoceruloplasminemia

2017 ◽  
pp. 97-100
Author(s):  
Pier Luigi Calvo ◽  
Marco Spada ◽  
Ivana Rabbone ◽  
Michele Pinon ◽  
Francesco Porta ◽  
...  
Keyword(s):  
Congenital Disorder ◽  
Congenital Disorder Of Glycosylation

Functional analysis of three splicing mutations identified in the PMM2 gene: Toward a new therapy for congenital disorder of glycosylation type Ia

2009 ◽  
Vol 30 (5) ◽  
pp. 795-803 ◽  
Author(s):  
Ana I. Vega ◽  
Celia Pérez-Cerdá ◽  
Lourdes R. Desviat ◽  
Gert Matthijs ◽  
Magdalena Ugarte ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Congenital Disorder ◽  
Congenital Disorder Of Glycosylation ◽  
New Therapy ◽  
Splicing Mutations ◽  
Type Ia

Skeletal Dysplasia and Myelopathy in Congenital Disorder of Glycosylation Type IA

2006 ◽  
Vol 148 (1) ◽  
pp. 115-117 ◽  
Author(s):  
Steven M. Schade van Westrum ◽  
Paul J. Nederkoorn ◽  
P. Richard Schuurman ◽  
Tom Vulsma ◽  
Marinus Duran ◽  
...  
Keyword(s):  
Skeletal Dysplasia ◽  
Congenital Disorder ◽  
Congenital Disorder Of Glycosylation ◽  
Type Ia

scholarly journals Bi-allelic variants in the ER quality control mannosidase gene EDEM3 cause a congenital disorder of glycosylation

2021 ◽  
Author(s):  
Daniel L. Polla ◽  
Andrew C. Edmondson ◽  
Sandrine Duvet ◽  
Michael E. March ◽  
Ana Berta Sousa ◽  
...  
Keyword(s):  
Quality Control ◽  
Congenital Disorder ◽  
Er Quality Control ◽  
Allelic Variants ◽  
Congenital Disorder Of Glycosylation

scholarly journals Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG

2019 ◽  
Author(s):  
Sangeetha Iyer ◽  
Feba S. Sam ◽  
Nina DiPrimio ◽  
Graeme Preston ◽  
Jan Verhejein ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Diabetic Neuropathy ◽  
Aldose Reductase ◽  
Reductase Inhibitor ◽  
Drug Repurposing ◽  
Polyol Pathway ◽  
Aldose Reductase Inhibitor ◽  
Congenital Disorder ◽  
Functional Studies ◽  
Congenital Disorder Of Glycosylation

AbstractPhosphomannomutase 2 deficiency, or PMM2-CDG, is the most common congenital disorder of glycosylation affecting over 1,000 patients globally. There are no approved drugs that treat the symptoms or root cause of PMM2-CDG. In order to identify clinically actionable compounds that boost human PMM2 enzyme function, we performed a multi-species drug repurposing screen using a first-ever worm model of PMM2-CDG followed by PMM2 enzyme functional studies in PMM2-CDG patient fibroblasts. Drug repurposing candidates from this study, and drug repurposing candidates from a previously published study using yeast models of PMM2-CDG, were tested for their effect on human PMM2 enzyme activity in PMM2-CDG fibroblasts. Of the 20 repurposing candidates discovered in the worm-based phenotypic screen, 12 are plant-based polyphenols. Insights from structure-activity relationships revealed epalrestat, the only antidiabetic aldose reductase inhibitor approved for use in humans, as a first-in-class PMM2 enzyme activator. Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains range from 30% to 400% over baseline depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations. We demonstrate that epalrestat is the first small molecule activator of PMM2 enzyme activity with the potential to treat peripheral neuropathy and correct the underlying enzyme deficiency in a majority of pediatric and adult PMM2-CDG patients.

scholarly journals Congenital disorder of glycosylation type Ia: a non-progressive encephalopathy associated with multisystemic involvement

2008 ◽  
Vol 66 (3a) ◽  
pp. 545-548 ◽  
Author(s):  
Jaime Moritz Brum ◽  
Isabela Maria Pinto de Oliveira Rizzo ◽  
Walquiria Domingues de Mello ◽  
Carlos Eduardo Speck-Martins
Keyword(s):  
Congenital Disorder ◽  
Congenital Disorder Of Glycosylation ◽  
Progressive Encephalopathy ◽  
Type Ia

scholarly journals Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null Mutation

2015 ◽  
pp. 7-12 ◽  
Author(s):  
Beyhan Tuysuz ◽  
Davut Pehlivan ◽  
Ahmet Özkök ◽  
Shalini Jhangiani ◽  
Cengiz Yalcinkaya ◽  
...  
Keyword(s):  
Congenital Disorder ◽  
Null Mutation ◽  
Congenital Disorder Of Glycosylation
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