title: Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
abstract: The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation. In this study, we describe the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG).
  
  
  
  Prospective natural history protocol.
  
  
  
  In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure. Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination. We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
  
  
  
  Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Christina
authors.identifier: 0000-0003-4705-6434
authors.initials: C
authors.lastname: Lam
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.|Division of Genetics and Metabolism, Children's National Medical Center, Washington, DC, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Division of Genetics and Developmental Biology, National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Krasnewich
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Toro
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lea
authors.initials: L
authors.lastname: Latham
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Wadih M
authors.identifier: 0000-0002-3771-6120
authors.initials: WM
authors.lastname: Zein
authors.affiliation: Electromyography Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Lehky
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Brewer
authors.affiliation: Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Eva H
authors.initials: EH
authors.lastname: Baker
authors.affiliation: Pediatric and Developmental Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland, USA.
authors.forename: Audrey
authors.identifier: 0000-0002-0489-9485
authors.initials: A
authors.lastname: Thurm
authors.affiliation: Pediatric and Developmental Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland, USA.
authors.forename: Cristan A
authors.identifier: 0000-0001-6878-5199
authors.initials: CA
authors.lastname: Farmer
authors.affiliation: Immunology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Rosenzweig
authors.affiliation: Genetics and Pathogenesis of Allergy Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jonathan J
authors.identifier: 0000-0002-2346-8189
authors.initials: JJ
authors.lastname: Lyons
authors.affiliation: Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Schreiber
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gropman
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Lingala
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.affiliation: Speech and Language Pathology Section, Department of Rehabilitation Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Solomon
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ellen
authors.identifier: 0000-0002-9418-3287
authors.initials: E
authors.lastname: Macnamara
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mariska
authors.identifier: 0000-0003-3863-073X
authors.initials: M
authors.lastname: Davids
authors.affiliation: Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, Irvine, California, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.|NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.|Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Wolfe
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D008297:Male; D009154:Mutation; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000172:deficiency / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D000418:Albumins; D002556:Cerebrospinal Fluid Proteins; D006023:Glycoproteins; C000622771:NGLY1 protein, human; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase