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Record W2912327695 · doi:10.1002/jimd.12055

Clinical, neuroradiological, and biochemical features of SLC35A2‐CDG patients

2019· article· en· W2912327695 on OpenAlexaff
Mari‐Anne Vals, Angel Ashikov, Pilvi Ilves, Dagmar Loorits, Qiang Zeng, Rita Barone, Karin Huijben, Jolanta Sykut‐Cegielska, Luísa Diogo, Abdallah F. Elias, Robert Greenwood, Stephanie Grünewald, Peter M. van Hasselt, Jiddeke M. van de Kamp, Grazia M.S. Mancini, A Oknińska, Sander Pajusalu, Pauline M. Rudd, Cecilie F. Rustad, Ramona Salvarinova, Bert B.A. de Vries, Nicole I. Wolf, Bobby G. Ng, Hudson H. Freeze, Dirk J. Lefeber, Katrin Õunap

Bibliographic record

VenueJournal of Inherited Metabolic Disease · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsUniversity of British ColumbiaBC Children's Hospital
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesHorizon 2020 Framework ProgrammeEesti TeadusagentuurNational Institutes of HealthNederlandse Organisatie voor Wetenschappelijk OnderzoekH2020 European Institute of Innovation and TechnologyZonMwEuropean Commission
KeywordsCorpus callosumHypotoniaEpilepsyAbnormalityMedicineHypsarrhythmiaHyperintensityPathologyEncephalopathyWhite matterPediatricsInternal medicineMagnetic resonance imagingRadiology

Abstract

fetched live from OpenAlex

SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. In view of the diagnostic challenges, we studied the clinical, neuroradiological, and biochemical features of 15 patients (11 females and 4 males) with SLC35A2-CDG from various centers. We describe nine novel pathogenic variations in SLC35A2. All affected individuals presented with a global developmental delay, and hypotonia, while 70% were nonambulatory. Epilepsy was present in 80% of the patients, and in EEG hypsarrhythmia and findings consistent with epileptic encephalopathy were frequently seen. The most common brain MRI abnormality was cerebral atrophy with delayed myelination and multifocal inhomogeneous abnormal patchy white matter hyperintensities, which seemed to be nonprogressive. Thin corpus callosum was also common, and all the patients had a corpus callosum shorter than normal for their age. Variable dysmorphic features and growth deficiency were noted. Biochemically, normal mucin type O-glycosylation and lipid glycosylation were found, while transferrin mass spectrometry was found to be more specific in the identification of SLC35A2-CDG, as compared to routine screening tests. Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, our data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.605
Threshold uncertainty score0.450

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.262
Teacher spread0.252 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations52
Published2019
Admission routes1
Has abstractyes

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