Globotriaosylsphingosine (lyso-Gb<sub>3</sub>) and analogues in plasma and urine of patients with Fabry disease and correlations with long-term treatment and genotypes in a nationwide female Danish cohort
Bibliographic record
Abstract
Introduction Recent studies showed the usefulness of globotriaosylsphingosine (lyso-Gb 3 ) and related analogues, deacylated forms of globotriaosylceramide (Gb 3 ), for high-risk screening, treatment monitoring and follow-up for patients with Fabry disease. Methods We evaluated Gb 3 , lyso-Gb 3 and analogues using tandem mass spectrometry in 57 women with Fabry disease followed during a period of 15.4 years. Twenty-one women were never treated and 36 received treatment (agalsidase-beta, n=30; agalsidase-alfa, n=5; or migalastat, n=1). Lyso-Gb 3 and analogues at m/z (−28), (−2), (+16), (+34) and (+50) were analysed in plasma and urine. Total Gb 3 and lyso-Gb 3 analogues at m/z (−12) and (+14) were evaluated in urine while the analogue at m/z (+18) was evaluated in plasma. Results A strong correlation between plasma and urine lyso-Gb 3 and analogue levels was revealed. Plasma and urine lyso-Gb 3 and analogue levels were not statistically different between patients carrying missense (n=49), nonsense (n=6) or deletion mutations (n=2). Never treated patients had lower plasma lyso-Gb 3 and analogues at m/z (−28), (−2), (+16), (+34) and the seven urinary lyso-Gb 3 analogues compared with pretreatment levels of the treated patients. A significant reduction of plasma lyso-Gb 3 and five analogues, as well as urine Gb 3 and six lyso-Gb 3 analogues, but not lyso-Gb 3 and lyso-Gb 3 at m/z (+50), was observed post-treatment with agalsidase-beta. The same tendency was observed with agalsidase-alfa. Conclusion Women with Fabry disease who started treatment based on clinical manifestations had higher lyso-Gb 3 and analogue biomarker levels than never treated women. This indicates that a biomarker cut-off could potentially be a decision tool for treatment initiation in women with Fabry disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".