Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions.

Autor:	Ng BG; Human Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., Eklund EA; Human Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.; Department of Clinical Sciences, Lund, Pediatrics, Lund University, Lund, Sweden., Shiryaev SA; Human Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., Dong YY; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Abbott MA; Department of Pediatrics, Baystate Children's Hospital, University of Massachusetts Medical School - Baystate, Springfield, Massachusetts, USA., Asteggiano C; CEMECO-CONICET, Children Hospital, School of Medicine, National University of Cordoba, Cordoba, Argentina.; Chair of Pharmacology, Catholic University of Cordoba, Cordoba, Argentina., Bamshad MJ; Department of Pediatrics, University of Washington, Seattle, Washington, USA.; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Barr E; Department of Human Genetics, Emory University, Atlanta, Georgia, USA., Bernstein JA; Stanford University School of Medicine, Stanford, California, USA.; Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, California, USA., Chelakkadan S; Monash Children's Hospital, Melbourne, Australia., Christodoulou J; Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Australia.; Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia., Chung WK; Department of Pediatrics, Columbia University, New York, New York, USA.; Department of Medicine, Columbia University, New York, New York, USA., Ciliberto MA; Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA., Cousin J; Section of Human Biochemical Genetics, National Human Genome Research Institute, Bethesda, Maryland, USA., Gardiner F; University of Melbourne, Austin Health, Melbourne, Australia., Ghosh S; Department of Pediatrics Division of Pediatric Neurology, University of Florida College of Medicine, Gainesville, Florida, USA., Graf WD; Division of Pediatric Neurology, Department of Pediatrics, Connecticut Children's; University of Connecticut, Farmington, Connecticut, USA., Grunewald S; Metabolic Medicine Department, Great Ormond Street Hospital, Institute of Child Health University College London, NIHR Biomedical Research Center, London, UK., Hammond K; Division of Pediatric Neurology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Hauser NS; Inova Translational Medicine Institute Division of Medical Genomics Inova Fairfax Hospital Falls Church, Virginia, USA., Hoganson GE; Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois, USA., Houck KM; Department of Pediatrics, Section of Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, Texas, USA., Kohler JN; Stanford University School of Medicine, Stanford, California, USA.; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA., Morava E; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA., Larson AA; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA., Liu P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; Baylor Genetics Laboratories, Houston, Texas, USA., Madathil S; Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA., McCormack C; Stanford University School of Medicine, Stanford, California, USA.; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA., Meeks NJL; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA., Miller R; Inova Translational Medicine Institute Division of Medical Genomics Inova Fairfax Hospital Falls Church, Virginia, USA., Monaghan KG; GeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA., Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Palculict TB; GeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA., Papazoglu GM; CEMECO-CONICET, Children Hospital, School of Medicine, National University of Cordoba, Cordoba, Argentina., Pletcher BA; Department of Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA., Scheffer IE; University of Melbourne, Austin Health, Melbourne, Australia.; University of Melbourne, Royal Children's Hospital, Florey and Murdoch Institutes, Melbourne, Australia., Schenone AB; Laboratorio de Neuroquimica 'Dr. N. A. Chamoles'-FESEN, Buenos Aires, Argentina., Schnur RE; GeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA., Si Y; GeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA., Rowe LJ; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA., Serrano Russi AH; Division of Medical Genetics Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.; Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Russo RS; Department of Human Genetics, Emory University, Atlanta, Georgia, USA., Thabet F; MercyOne Pediatric Neurology, Des Moines, Iowa, USA., Tuite A; Department of Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA., Villanueva MM; Laboratorio de Neuroquimica 'Dr. N. A. Chamoles'-FESEN, Buenos Aires, Argentina., Wang RY; Division of Metabolic Disorders, Children's Hospital of Orange County, Orange, California, USA.; Department of Pediatrics, University of California-Irvine, Orange, California, USA., Webster RI; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital, Westmead, Australia.; Kids Neuroscience Centre, The Children's Hospital, Westmead, Australia., Wilson D; Netcare Sunninghill Hospital, Sandton, South Africa.; Nelson Mandela Children's Hospital, Johannesburg, South Africa., Zalan A; Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois, USA., Wolfe LA; Undiagnosed Diseases Program, Common Fund, National Institutes of Health, Bethesda, Maryland, USA., Rosenfeld JA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; Baylor Genetics Laboratories, Houston, Texas, USA., Rhodes L; GeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA., Freeze HH; Human Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Jazyk:	angličtina
Zdroj:	Journal of inherited metabolic disease [J Inherit Metab Dis] 2020 Nov; Vol. 43 (6), pp. 1333-1348. Date of Electronic Publication: 2020 Aug 05.
DOI:	10.1002/jimd.12290
Abstrakt:	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. (© 2020 SSIEM.)
Databáze:	MEDLINE
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