Treatment Efficiency in Gaucher Patients Can Reliably Be Monitored by Quantification of Lyso-Gb1 Concentrations in Dried Blood Spots.

Autor: Cozma C; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Cullufi P; Pediatric Department, University Hospital 'Mother Teresa', 1000 Tirana, Albania., Kramp G; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Hovakimyan M; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Velmishi V; Pediatric Department, University Hospital 'Mother Teresa', 1000 Tirana, Albania., Gjikopulli A; Pediatric Department, University Hospital 'Mother Teresa', 1000 Tirana, Albania., Tomori S; Pediatric Department, University Hospital 'Mother Teresa', 1000 Tirana, Albania., Fischer S; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Oppermann S; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Grittner U; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany.; Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany., Bauer P; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Beetz C; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany., Rolfs A; CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Jun 27; Vol. 21 (13). Date of Electronic Publication: 2020 Jun 27.
DOI: 10.3390/ijms21134577
Abstrakt: Gaucher disease (GD) is a lysosomal storage disorder that responds well to enzyme replacement therapy (ERT). Certain laboratory parameters, including blood concentration of glucosylsphingosine (Lyso-Gb1), the lyso-derivate of the common glycolipid glucocerebroside, correlate with clinical improvement and are therefore considered candidate-monitoring biomarkers. Whether they can indicate a reduction or loss of treatment efficiency, however, has not been systematically addressed for obvious reasons. We established and validated measurement of Lyso-Gb1 from dried blood spots (DBSs) by mass spectrometry. We then characterized the assay's longitudinal performance in 19 stably ERT-treated GD patients by dense monitoring over a 3-year period. The observed level of fluctuation was accounted for in the subsequent development of a unifying data normalization concept. The resulting approach was eventually applied to data from Lyso-Gb1 measurements after an involuntary treatment break for all 19 patients. It enabled separation of the "under treatment" versus "not under treatment" conditions with high sensitivity and specificity. We conclude that Lyso-Gb1 determination from DBSs indicates treatment issues already at an early stage before clinical consequences arise. In addition to its previously shown diagnostic utility, Lyso-Gb1 thereby qualifies as a monitoring biomarker in GD patients.
Databáze: MEDLINE
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