Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.
Abstract
Historically, disease burden and treatment responses in patients with Gaucher disease
(GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase
(CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO
is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring.
Furthermore, studies measuring lyso-Gb1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT)
and/or substrate reduction therapy (SRT) reported as group data show a reduction in
both analytes, yet individualized patient data are generally unavailable. We describe
seven patients on long-term treatment with longitudinal clinical data with monitoring
based on current treatment guidelines. We present four patients who exhibit stable
disease with normalized CHITO despite elevated lyso-Gb1. We present one patient who transitioned from ERT to SRT due to lack of a clinical
response with life-threatening thrombocytopenia who responded with marked improvement
in platelets, and normalized levels of both CHITO and lyso-Gb1. Finally, we present two ERT to SRT switch patients with stable disease on ERT who
exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and
lyso-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value
when CHITO is normal and thus uninformative. We highlight the personalized medicine
approach needed to optimize treatment outcomes and recommendations for these patients.
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https://hdl.handle.net/10161/26419Published Version (Please cite this version)
10.3390/ijms232314938Publication Info
Gayed, Matthew M; Jung, Seung-Hye; Huggins, Erin; Rodriguez-Rassi, Eleanor; DeArmey,
Stephanie; Kishnani, Priya Sunil; & Stiles, Ashlee R (2022). Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.
International journal of molecular sciences, 23(23). pp. 14938. 10.3390/ijms232314938. Retrieved from https://hdl.handle.net/10161/26419.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Priya Sunil Kishnani
Chen Family Distinguished Professor of Pediatrics
RESEARCH INTERESTS A multidisciplinary approach to care of individuals with genetic
disorders in conjunction with clinical and bench research that contributes to: 1)
An understanding of the natural history and delineation of long term complications
of genetic disorders with a special focus on liver Glycogen storage disorders, lysosomal
disorders with a special focus on Pompe disease, Down syndrome and hypophosphatasia2) )
The development of new therapies such
Ashlee R. Stiles
Associate Professor of Pediatrics
Dr. Stiles is a fellow of the American College of Medical Genetics and Genomics trained
in clinical biochemical genetics and molecular genetics. She is co-director of the
Duke University Health System Biochemical Genetics Laboratory and external Referral
Laboratory. In her work with the Biochemical Genetics laboratory, her research interests
focus on improving and developing laboratory diagnostics for rare inborn errors of
metabolism. In her role as director of the Referral laboratory, she wo
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