Expanding the phenotype, genotype and biochemical knowledge of ALG3‐CDG
| Autor: | Eissa Faqeih, Jennifer Friedman, Hudson H. Freeze, Kierstin N Keller, Miao He, Earnest James Paul Daniel, Jie Chen, Hind Alsharhan, Eniko K. Pivnick, Christina Lam, Nicole Engelhardt, Amal Alhashem, Michael J. Bamshad, Deborah A. Nickerson, Pengfei Liu, Kimiyo Raymond, Pamela A Mazzeo, Jill A. Rosenfeld, Bobby G. Ng, Andrew C. Edmondson |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Glycan Microcephaly Adolescent Genotype Bioinformatics Mannosyltransferases Article Young Adult Epilepsy Congenital Disorders of Glycosylation Genetics medicine Humans Endocrine system Genetics (clinical) Immunodeficiency biology Neural tube defect business.industry Infant Newborn Neural tube Infant medicine.disease Hypotonia carbohydrates (lipids) Phenotype medicine.anatomical_structure Child Preschool biology.protein Female medicine.symptom business |
| Zdroj: | J Inherit Metab Dis |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1002/jimd.12367 |
| Popis: | Congenital disorders of glycosylation (CDGs) are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid biosynthesis that cause multisystem diseases. Individuals with ALG3-CDG frequently exhibit severe neurological involvement (epilepsy, microcephaly, and hypotonia), ocular anomalies, dysmorphic features, skeletal anomalies, and feeding difficulties. We present 10 unreported individuals diagnosed with ALG3-CDG based on molecular and biochemical testing with 11 novel variants in ALG3, bringing the total to 40 reported individuals. In addition to the typical multisystem disease seen in ALG3-CDG, we expand the symptomatology of ALG3-CDG to now include endocrine abnormalities, neural tube defects, mild aortic root dilatation, immunodeficiency, and renal anomalies. N-glycan analyses of these individuals showed combined deficiencies of hybrid glycans and glycan extension beyond Man(5)GlcNAc(2) consistent with their truncated lipid-linked precursor oligosaccharides. This spectrum of N-glycan changes is unique to ALG3-CDG. These expanded features of ALG3-CDG facilitate diagnosis and suggest that optimal management should include baseline endocrine, renal, cardiac, and immunological evaluation at the time of diagnosis and with ongoing monitoring. |
| Databáze: | OpenAIRE |
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