Evidence map›Paper›PMID 32681751›Full record

ArticleJournal of inherited metabolic disease2020

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

Bobby G Ng, Erik A Eklund, Sergey A Shiryaev, Yin Y Dong, Mary-Alice Abbott, Carla Asteggiano, Michael J Bamshad, Eileen Barr, Jonathan A Bernstein, Shabeed Chelakkadan and 44 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of inherited metabolic disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02450851 recruitingnot on this map

Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

TypeobservationalSponsorNational Human Genome Research Institute (NHGRI)Ran2015 to 2028Enrolled20,000ConditionsGenetic Disease
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. NovelHuman mutation · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Biallelic USP14 variants cause a syndromic neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2024
    Article
  13. Long-term outcomes in ALG13-Congenital Disorder of Glycosylation.American journal of medical genetics. Part A · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

54 authors at 20 institutions in 6 countries.

Bobby G NgHuman Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.ORCID 0000-0003-0649-848X
Erik A EklundHuman Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Sergey A ShiryaevHuman Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Yin Y DongNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Mary-Alice AbbottDepartment of Pediatrics, Baystate Children's Hospital, University of Massachusetts Medical School - Baystate, Springfield, Massachusetts, USA.
Carla AsteggianoCEMECO-CONICET, Children Hospital, School of Medicine, National University of Cordoba, Cordoba, Argentina.
Michael J BamshadDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Eileen BarrDepartment of Human Genetics, Emory University, Atlanta, Georgia, USA.
Jonathan A BernsteinStanford University School of Medicine, Stanford, California, USA.
Shabeed ChelakkadanMonash Children's Hospital, Melbourne, Australia.
John ChristodoulouBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
Wendy K ChungDepartment of Pediatrics, Columbia University, New York, New York, USA.
Michael A CilibertoDepartment of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Janice CousinSection of Human Biochemical Genetics, National Human Genome Research Institute, Bethesda, Maryland, USA.
Fiona GardinerUniversity of Melbourne, Austin Health, Melbourne, Australia.
Suman GhoshDepartment of Pediatrics Division of Pediatric Neurology, University of Florida College of Medicine, Gainesville, Florida, USA.
William D GrafDivision of Pediatric Neurology, Department of Pediatrics, Connecticut Children's; University of Connecticut, Farmington, Connecticut, USA.
Stephanie GrunewaldMetabolic Medicine Department, Great Ormond Street Hospital, Institute of Child Health University College London, NIHR Biomedical Research Center, London, UK.
Katherine HammondDivision of Pediatric Neurology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Natalie S HauserInova Translational Medicine Institute Division of Medical Genomics Inova Fairfax Hospital Falls Church, Virginia, USA.
George E HogansonDepartment of Pediatrics, University of Illinois at Chicago, Chicago, Illinois, USA.
Kimberly M HouckDepartment of Pediatrics, Section of Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Jennefer N KohlerStanford University School of Medicine, Stanford, California, USA.
Eva MoravaDepartment of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
Austin A LarsonSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Pengfei LiuDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Sujana MadathilDepartment of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Colleen McCormackStanford University School of Medicine, Stanford, California, USA.
Naomi J L MeeksSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Rebecca MillerInova Translational Medicine Institute Division of Medical Genomics Inova Fairfax Hospital Falls Church, Virginia, USA.
Kristin G MonaghanGeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA.
Deborah A NickersonDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Timothy Blake PalculictGeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA.
Gabriela Magali PapazogluCEMECO-CONICET, Children Hospital, School of Medicine, National University of Cordoba, Cordoba, Argentina.
Beth A PletcherDepartment of Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
Ingrid E SchefferUniversity of Melbourne, Austin Health, Melbourne, Australia.
Andrea Beatriz SchenoneLaboratorio de Neuroquimica "Dr. N. A. Chamoles"-FESEN, Buenos Aires, Argentina.
Rhonda E SchnurGeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA.
Yue SiGeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA.
Leah J RoweSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Alvaro H Serrano RussiDivision of Medical Genetics Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.
Rossana Sanchez RussoDepartment of Human Genetics, Emory University, Atlanta, Georgia, USA.
Farouq ThabetMercyOne Pediatric Neurology, Des Moines, Iowa, USA.
Allysa TuiteDepartment of Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
María Mercedes VillanuevaLaboratorio de Neuroquimica "Dr. N. A. Chamoles"-FESEN, Buenos Aires, Argentina.
Raymond Y WangDivision of Metabolic Disorders, Children's Hospital of Orange County, Orange, California, USA.
Richard I WebsterT.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital, Westmead, Australia.
Dorcas WilsonNetcare Sunninghill Hospital, Sandton, South Africa.
Alice ZalanDepartment of Pediatrics, University of Illinois at Chicago, Chicago, Illinois, USA.
Undiagnosed Diseases Network, University of Washington Center for Mendelian Genomics (UW-CMG)
Lynne A WolfeUndiagnosed Diseases Program, Common Fund, National Institutes of Health, Bethesda, Maryland, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Lindsay RhodesGeneDx, Inc. Laboratory, Gaithersburg, Maryland, USA.
Hudson H FreezeHuman Genetics Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
GenVec · USBaylor College of Medicine · USSanford Burnham Prebys Medical Discovery Institute · USStanford University · USUniversity of Colorado Anschutz Medical Campus · USEmory University · USInova Fairfax Hospital · USRutgers, The State University of New Jersey · USUniversity of Illinois Chicago · USUniversity of Iowa Hospitals and Clinics · USUniversity of Washington · USBaystate Medical Center · USChildren's Hospital at Westmead · AUChildren's Hospital of Orange County · USColumbia University · USConsejo Nacional de Investigaciones Científicas y Técnicas · ARGreat Ormond Street Hospital · GBLund University · SEMayo Clinic · USMercy Medical Center · US

Funding

UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
Pilot and Feasibility CoreU54NS115198 · NINDS · MAYO CLINIC ROCHESTER · PI MORAVA-KOZICZ, EVA · 2019 to 2023
$8.2M
Stanford Center for Undiagnosed DiseasesU01HG007708 · NHGRI · STANFORD UNIVERSITY · PI ASHLEY, EUAN A, BERNSTEIN, JONATHAN ADAM · 2014 to 2018
$8.0M
New Congenital Disorders of Glycosylation: Therapy and ModelsR01DK099551 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Hudson H. Freeze · 2014 to 2026
$6.7M
What comes next? Engaging stakeholders in governance of participant data and relationships during the sunset of large genomic medicine research initiativesU01HG010218 · NHGRI · STANFORD UNIVERSITY · PI ASHLEY, EUAN A, BERNSTEIN, JONATHAN ADAM · 2018 to 2022
$6.3M
NHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9M
Medical Research Council MR/S007180/1NHGRI NIH HHS U01 HG007708NHGRI NIH HHS U01 HG010218NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006493NIDDK NIH HHS R01 DK099551NINDS NIH HHS U54 NS115198
6 · The paper itself

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.

Indexed as

BiomarkersChild, PreschoolCongenital Disorders of GlycosylationDiet, KetogenicFemaleGlycosylationHumansInfantMaleMutationN-AcetylglucosaminyltransferasesSpasms, InfantileTransferrinALG13 protein, humanBiomarkersN-AcetylglucosaminyltransferasesTransferrincongenital disorders of glycosylationepilepsyN-linked glycosylationwhole exome sequencing

Identifiers

PMID32681751
PMCPMC7722193
OpenAlexW3042529998

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.