Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/27731
Title: Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions.
Austin Authors: Ng, Bobby G;Eklund, Erik A;Shiryaev, Sergey A;Dong, Yin Y;Abbott, Mary-Alice;Asteggiano, Carla;Bamshad, Michael J;Barr, Eileen;Bernstein, Jonathan A;Chelakkadan, Shabeed;Christodoulou, John;Chung, Wendy K;Ciliberto, Michael A;Cousin, Janice;Gardiner, Fiona;Ghosh, Suman;Graf, William D;Grunewald, Stephanie;Hammond, Katherine;Hauser, Natalie S;Hoganson, George E;Houck, Kimberly M;Kohler, Jennefer N;Morava, Eva;Larson, Austin A;Liu, Pengfei;Madathil, Sujana;McCormack, Colleen;Meeks, Naomi J L;Miller, Rebecca;Monaghan, Kristin G;Nickerson, Deborah A;Palculict, Timothy Blake;Papazoglu, Gabriela Magali;Pletcher, Beth A;Scheffer, Ingrid E ;Schenone, Andrea Beatriz;Schnur, Rhonda E;Si, Yue;Rowe, Leah J;Serrano Russi, Alvaro H;Russo, Rossana Sanchez;Thabet, Farouq;Tuite, Allysa;Villanueva, María Mercedes;Wang, Raymond Y;Webster, Richard I;Wilson, Dorcas;Zalan, Alice;Wolfe, Lynne A;Rosenfeld, Jill A;Rhodes, Lindsay;Freeze, Hudson H
Affiliation: Department of Medicine, Columbia University, New York, New York, USA
Department of Pediatrics, Columbia University, New York, New York, USA
Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA
Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Department of Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA
Department of Genome Sciences, University of Washington, Seattle, Washington, USA
Department of Pediatrics, University of Washington, Seattle, Washington, USA
Department of Pediatrics, Baystate Children's Hospital, University of Massachusetts Medical School - Baystate, Springfield, Massachusetts, USA
Department of Human Genetics, Emory University, Atlanta, Georgia, USA
Monash Children's Hospital, Melbourne, Australia
GeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA
Baylor Genetics Laboratories, Houston, Texas, USA
Inova Translational Medicine Institute Division of Medical Genomics Inova Fairfax Hospital Falls Church, Virginia, USA
MercyOne Pediatric Neurology, Des Moines, Iowa, USA
Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California, USA
Department of Pediatrics, University of California-Irvine, Orange, California, USA
Division of Metabolic Disorders, Children's Hospital of Orange County, Orange, California, USA
Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Division of Medical Genetics Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
Stanford University School of Medicine, Stanford, California, USA
Chair of Pharmacology, Catholic University of Cordoba, Cordoba, Argentina, USA
CEMECO-CONICET, Children Hospital, School of Medicine, National University of Cordoba, Cordoba, Argentina
Department of Clinical Sciences, Lund, Pediatrics, Lund University, Lund, Sweden, USA
Human Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA
Kids Neuroscience Centre, The Children's Hospital, Westmead, Australia
T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital, Westmead, Australia
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
Division of Pediatric Neurology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA
Division of Pediatric Neurology, Department of Pediatrics, Connecticut Children's; University of Connecticut, Farmington, Connecticut, USA
Department of Pediatrics Division of Pediatric Neurology, University of Florida College of Medicine, Gainesville, Florida, USA
Section of Human Biochemical Genetics, National Human Genome Research Institute, Bethesda, Maryland, USA
Undiagnosed Diseases Program, Common Fund, National Institutes of Health, Bethesda, Maryland, USA
Nelson Mandela Children's Hospital, Johannesburg, South Africa, USA
Netcare Sunninghill Hospital, Sandton, South Africa
Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA
Department of Pediatrics, Section of Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, Texas, USA
Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois, USA
University of Melbourne, Royal Children's Hospital, Florey and Murdoch Institutes, Melbourne, Australia
Austin Health
Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Australia
Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK, USA
Metabolic Medicine Department, Great Ormond Street Hospital, Institute of Child Health University College London, NIHR Biomedical Research Center, London, UK, USA
CEMECO-CONICET, Children Hospital, School of Medicine, National University of Cordoba, Cordoba, Argentina, USA
Laboratorio de Neuroquimica "Dr. N. A. Chamoles"-FESEN, Buenos Aires, Argentina, USA
Issue Date: Nov-2020
metadata.dc.date: 2020-08-05
Publication information: Journal of Inherited Metabolic Disease 2020; 43(6): 1333-1348
Abstract: Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.
URI: https://ahro.austin.org.au/austinjspui/handle/1/27731
DOI: 10.1002/jimd.12290
ORCID: 0000-0003-0649-848X
PubMed URL: 32681751
Type: Journal Article
Subjects: N-linked glycosylation
congenital disorders of glycosylation
epilepsy
whole exome sequencing
Appears in Collections:Journal articles

Show full item record

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.