Evidence map›Paper›PMID 32852845›Full record

ArticleJournal of inherited metabolic disease2020

N-glycome analysis detects dysglycosylation missed by conventional methods in SLC39A8 deficiency.

Julien H Park, Robert G Mealer, Abdallah F Elias, Susanne Hoffmann, Marianne Grüneberg, Saskia Biskup, Manfred Fobker, Jaclyn Haven, Ute Mangels, Janine Reunert and 6 more

Open access · hybridAbstract readMulticenter Study
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. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 32% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
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

16 authors at 8 institutions in 3 countries.

Julien H ParkDepartment of Clinical Sciences, Neurosciences, Umeå University, Umeå, Sweden.ORCID 0000-0003-2305-9948
Robert G MealerPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-5963-2836
Abdallah F EliasDepartment of Medical Genetics, Shodair Children's Hospital, Helena, Montana, USA.ORCID 0000-0003-0595-1035
Susanne HoffmannZentrum für Sozial- und Neuropädiatrie, Vivantes Klinikum Neukölln, Berlin, Germany.
Marianne GrünebergDepartment of General Pediatrics, University of Münster, Münster, Germany.
Saskia BiskupCeGAT GmbH and Praxis für Humangenetik Tübingen, Tübingen, Germany.
Manfred FobkerCenter for Laboratory Medicine, University Hospital Münster, Münster, Germany.
Jaclyn HavenDepartment of Medical Genetics, Shodair Children's Hospital, Helena, Montana, USA.
Ute MangelsDepartment of General Pediatrics, University of Münster, Münster, Germany.
Janine ReunertDepartment of General Pediatrics, University of Münster, Münster, Germany.
Stephan RustDepartment of General Pediatrics, University of Münster, Münster, Germany.
Jonathan SchoofDepartment of Medical Genetics, Shodair Children's Hospital, Helena, Montana, USA.
Corbin SchwankeDepartment of Medical Genetics, Shodair Children's Hospital, Helena, Montana, USA.
Jordan W SmollerPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-0381-6334
Richard D CummingsNational Center for Functional Glycomics, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-8918-5034
Thorsten MarquardtDepartment of General Pediatrics, University of Münster, Münster, Germany.ORCID 0000-0002-9982-2981
University of Münster · DEShodair Children's Hospital · USBroad Institute · USBeth Israel Deaconess Medical Center · USPraxis für Humangenetik Tübingen · DEUniversity Hospital Münster · DEUniversity of Utah · USVivantes Klinikum · DE

Funding

Translational Neuroscience Training for CliniciansT32MH112485 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI BUCKNER, RANDY L, ROFFMAN, JOSHUA LAWRENCE · 2018 to 2022
$1.7M
NIMH NIH HHS T32 MH112485
6 · The paper itself

Abstract

Congenital disorders of glycosylation (CDG) are a growing group of inborn metabolic disorders with multiorgan presentation. SLC39A8-CDG is a severe subtype caused by biallelic mutations in the manganese transporter SLC39A8, reducing levels of this essential cofactor for many enzymes including glycosyltransferases. The current diagnostic standard for disorders of N-glycosylation is the analysis of serum transferrin. Exome and Sanger sequencing were performed in two patients with severe neurodevelopmental phenotypes suggestive of CDG. Transferrin glycosylation was analyzed by high-performance liquid chromatography (HPLC) and isoelectric focusing in addition to comprehensive N-glycome analysis using matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS). Atomic absorption spectroscopy was used to quantify whole blood manganese levels. Both patients presented with a severe, multisystem disorder, and a complex neurological phenotype. Magnetic resonance imaging (MRI) revealed a Leigh-like syndrome with bilateral T2 hyperintensities of the basal ganglia. In patient 1, exome sequencing identified the previously undescribed homozygous variant c.608T>C [p.F203S] in SLC39A8. Patient 2 was found to be homozygous for c.112G>C [p.G38R]. Both individuals showed a reduction of whole blood manganese, though transferrin glycosylation was normal. N-glycome using MALDI-TOF MS identified an increase of the asialo-agalactosylated precursor N-glycan A2G1S1 and a decrease in bisected structures. In addition, analysis of heterozygous CDG-allele carriers identified similar but less severe glycosylation changes. Despite its reliance as a clinical gold standard, analysis of transferrin glycosylation cannot be categorically used to rule out SLC39A8-CDG. These results emphasize that SLC39A8-CDG presents as a spectrum of dysregulated glycosylation, and MS is an important tool for identifying deficiencies not detected by conventional methods.

Indexed as

AdolescentBasal GangliaCation Transport ProteinsChildChild, PreschoolChromatography, High Pressure LiquidCongenital Disorders of GlycosylationExome SequencingFemaleGlycosylationHumansInfantMagnetic Resonance ImagingMaleManganeseMass SpectrometryCation Transport ProteinsManganeseSLC39A8 protein, humanTransferrincongenital disorders of glycosylationglycosylationMALDI-TOF MSmanganeseSLC39A8

Identifiers

PMID32852845
PMCPMC8086894
OpenAlexW3081485285

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.