Insights into the Value of Lyso-Gb1 as a Predictive Biomarker in Treatment-Naïve Patients with Gaucher Disease Type 1 in the LYSO-PROOF Study.

Autor: Curado F; CENTOGENE GmbH, 18055 Rostock, Germany., Rösner S; CENTOGENE GmbH, 18055 Rostock, Germany., Zielke S; CENTOGENE GmbH, 18055 Rostock, Germany., Westphal G; CENTOGENE GmbH, 18055 Rostock, Germany., Grittner U; Berlin Institute of Health, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.; Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Skrahina V; Rhythm Pharmaceuticals Inc., 20095 Hamburg, Germany., Alasel M; CENTOGENE GmbH, 18055 Rostock, Germany., Malik AM; CENTOGENE GmbH, 18055 Rostock, Germany., Beetz C; CENTOGENE GmbH, 18055 Rostock, Germany., Böttcher T; CENTOGENE GmbH, 18055 Rostock, Germany., Barel G; CENTOGENE GmbH, 18055 Rostock, Germany., Sah AP; CENTOGENE GmbH, 18055 Rostock, Germany., Dinur T; Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel., Anjum N; The Children's Hospital and University of Child Health Sciences, Lahore 54600, Pakistan., Ichraf Q; Children Hospital's Rabat, Neuropediatric-Metabolic, Rabat 6527, Morocco., Kriouile Y; Children Hospital's Rabat, Neuropediatric-Metabolic, Rabat 6527, Morocco., Hadipour Z; Soodbakhash Poly Clinic, Atiyeh Hospital, Tehran 1416753955, Iran.; Medical Genetics Department, Pars Research Center & Hospital, Tehran 1416753955, Iran., Hadipour F; Soodbakhash Poly Clinic, Atiyeh Hospital, Tehran 1416753955, Iran.; Medical Genetics Department, Pars Research Center & Hospital, Tehran 1416753955, Iran., Revel-Vilk S; Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel., Cozma C; CENTOGENE GmbH, 18055 Rostock, Germany., Hartkamp J; CENTOGENE GmbH, 18055 Rostock, Germany., Cheema H; The Children's Hospital and University of Child Health Sciences, Lahore 54600, Pakistan., Zimran A; Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel., Bauer P; CENTOGENE GmbH, 18055 Rostock, Germany.; Medical Faculty, University of Rostock, 18057 Rostock, Germany., Rolfs A; Medical Faculty, University of Rostock, 18057 Rostock, Germany.; Agyany Pharmaceutics Ltd., Jerusalem 9103102, Israel.; RCV Rare Disease GmbH, 10115 Berlin, Germany.
Jazyk: angličtina
Zdroj: Diagnostics (Basel, Switzerland) [Diagnostics (Basel)] 2023 Aug 30; Vol. 13 (17). Date of Electronic Publication: 2023 Aug 30.
DOI: 10.3390/diagnostics13172812
Abstrakt: Gaucher disease (GD) is a rare autosomal recessive disorder arising from bi-allelic variants in the GBA1 gene, encoding glucocerebrosidase. Deficiency of this enzyme leads to progressive accumulation of the sphingolipid glucosylsphingosine (lyso-Gb1). The international, multicenter, observational "Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease"-LYSO-PROOF study succeeded in enrolling a cohort of 160 treatment-naïve GD patients from diverse geographic regions and evaluated the potential of lyso-Gb1 as a specific biomarker for GD. Using genotypes based on established classifications for clinical presentation, patients were stratified into type 1 GD ( n = 114) and further subdivided into mild ( n = 66) and severe type 1 GD ( n = 48). Due to having previously unreported genotypes, 46 patients could not be classified. Though lyso-Gb1 values at enrollment were widely distributed, they displayed a moderate and statistically highly significant correlation with disease severity measured by the GD-DS3 scoring system in all GD patients (r = 0.602, p < 0.0001). These findings support the utility of lyso-Gb1 as a sensitive biomarker for GD and indicate that it could help to predict the clinical course of patients with undescribed genotypes to improve personalized care in the future.
Databáze: MEDLINE
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