A Case of UDP-Galactose 4′-Epimerase Deficiency Associated with Dyshematopoiesis and Atrioventricular Valve Malformations: An Exceptional Clinical Phenotype Explained by Altered N-Glycosylation with Relative Preservation of the Leloir Pathway
| Autor: | Anuj Jayakar, Parul Jayakar, Jun Sasaki, Jorge R Galvez-Silva, Anthony J. Febres-Aldana², Meredith S. Wright, Christopher A. Febres-Aldana, Michelin Janvier, Liset Pelaez, Magaly Diaz-Barbosa, Daria Salyakina, Ossama M. Maher, Bala R Totapally |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Atrioventricular valve Glycosylation Atrioventricular valve morphogenesis 030305 genetics & heredity Galactosemia Biology Compound heterozygosity medicine.disease Bioinformatics Hypotonia carbohydrates (lipids) Leloir pathway 03 medical and health sciences chemistry.chemical_compound chemistry Novel Insights from Clinical Practice Failure to thrive Genetics medicine medicine.symptom Genetics (clinical) 030304 developmental biology |
| Zdroj: | Mol Syndromol |
| ISSN: | 1661-8777 1661-8769 |
| DOI: | 10.1159/000511343 |
| Popis: | The generalized form of UDP-galactose-4′-epimerase (GALE) deficiency causes hypotonia, failure to thrive, cataracts, and liver failure. Individuals with non-generalized forms may remain asymptomatic with uncertain long-term outcomes. We report a 2-year-old child compound heterozygous for GALE p.R51W/p.G237D who never developed symptoms of classic galactosemia but has a history of congenital combined mitral and tricuspid valve malformation and pyloric stenosis, and presented with pancytopenia. Variant pathogenicity was supported by predictive computational tools and decreased GALE activity measured in erythrocytes. GALE function extends to the biosynthesis of glycans by epimerization of UDP-N-acetyl-galactosamine and -glucosamine. Interrogation of the Gene Ontology consortium database revealed several putative proteins involved in normal hematopoiesis and atrioventricular valve morphogenesis, requiring N-glycosylation for adequate functionality. We hypothesize that by limiting substrate supply due to GALE deficiency, alterations in N-linked protein glycosylation can explain the patient’s phenotype. |
| Databáze: | OpenAIRE |
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