Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG.

Autor: Alsharhan H; Department of Pediatrics, Division of Human Genetics, Section of Metabolism, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait., Ng BG; Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., Daniel EJP; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Friedman J; Division of Neurosciences and Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, California, USA., Pivnick EK; Department of Pediatrics, Division of Medical Genetics, University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, USA., Al-Hashem A; Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Faqeih EA; Section of Medical Genetics, Children's Specialist Hospital King Fahad Medical City, Riyadh, Saudi Arabia., Liu P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; Baylor Genetics Laboratories, Houston, Texas, USA., Engelhardt NM; Department of Pediatrics, Division of Human Genetics, Section of Metabolism, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Keller KN; Department of Pediatrics, Division of Human Genetics, Section of Metabolism, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Chen J; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Mazzeo PA; Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Rosenfeld JA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; Baylor Genetics Laboratories, Houston, Texas, USA., Bamshad MJ; Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.; Brotman-Baty Institute, Seattle, Washington, USA., Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.; Brotman-Baty Institute, Seattle, Washington, USA., Raymond KM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Freeze HH; Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., He M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Edmondson AC; Department of Pediatrics, Division of Human Genetics, Section of Metabolism, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Lam C; Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.; Center of Integrated Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2021 Jul; Vol. 44 (4), pp. 987-1000. Date of Electronic Publication: 2021 Mar 01.
DOI: 10.1002/jimd.12367
Abstrakt: 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.
(© 2021 SSIEM.)
Databáze: MEDLINE
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