Coagulation abnormalities and vascular complications are common in PGM1-CDG
Bibliographic record
Abstract
Phosphoglucomutase-1-congenital disorder of glycosylation (PGM1-CDG) is a rare genetic disorder caused by biallelic variants in the PGM1 gene, leading to the deficiency of the PGM1 enzyme. The most common clinical presentations include muscle involvement, failure to thrive, cleft palate, and cardiac involvement. Abnormal serum N-glycosylation, hypoglycemia, and liver function abnormalities including coagulation abnormalities are the most common laboratory abnormalities. While PGM1-CDG has been extensively studied, little is known about the extent of the coagulation abnormalities in individuals with PGM1-CDG. Unlike most CDG, some symptoms of PGM1-CDG are treatable with D-galactose (D-gal) supplementation, though reliable clinical endpoints are necessary to appropriately evaluate the potential improvement with D-gal in PGM1-CDG. Here, we aimed to describe the incidence of coagulation abnormalities in PGM1-CDG and their evolution, their relation to clinical events, and the ability of D-gal treatment to improve them. A retrospective analysis was conducted on 73 reported individuals. All individuals had a molecularly confirmed PGM1-CDG diagnosis. All incidences of antithrombin (AT), aPTT, PT, factor (F) XI, FX, FIX, FVII, protein C and protein S data and major clinical events related to coagulation abnormalities, were collected. Coagulation information was available for only 58.9 % of the reported individuals, out of which 67.4 % of PGM1-CDG individuals were reported to have abnormalities. The most frequently observed abnormality was AT (mean: 30.8% R:80-120 %) deficiency. Four individuals had major thrombotic events. Coagulation status on D-gal treatment, were reported in 19 individuals. Several factors showed improvement including AT (mean: 64.5 %), indicating galactose is beneficial in treating coagulation abnormalities in PGM1-CDG. Due to the scarcity of the reported data on coagulation parameters, we also evaluated data collected in sixteen PGM1-CDG individuals enrolled in the FCDGC Natural History Study. Longitudinal data showed improvements in several coagulant parameters and disease severity improved for almost all patients of whom we had multiple datapoints on D-gal. AT showed significant improvement on D-gal. We conclude that coagulation abnormalities are frequently present in PGM1-CDG and show improvement on D-gal. We recommend coagulation parameters should be routinely checked in individuals with PGM1-CDG or suspected of having PGM1-CDG. Finally, AT may be used as a primary or secondary clinical endpoint for upcoming clinical trials in PGM1-CDG individuals.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".