Browsing by Author "Stiles, Ashlee R"

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    Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.
    (International journal of molecular sciences, 2022-11) Gayed, Matthew M; Jung, Seung-Hye; Huggins, Erin; Rodriguez-Rassi, Eleanor; DeArmey, Stephanie; Kishnani, Priya Sunil; Stiles, Ashlee R
    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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    The designated record set for clinical genetic and genomic testing: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG).
    (Genetics in medicine : official journal of the American College of Medical Genetics, 2022-12) Tayeh, Marwan K; Chen, Margaret; Fullerton, Stephanie M; Gonzales, Patrick R; Huang, Samuel J; Massingham, Lauren J; O'Daniel, Julianne M; Stewart, Douglas R; Stiles, Ashlee R; Evans, Barbara J; ACMG Laboratory Quality Assurance Committee and the ACMG Social, Ethical and Legal Issues Committee. Electronic address: documents@acmg.net
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    The role of glucosylsphingosine as an early indicator of disease progression in early symptomatic type 1 Gaucher disease.
    (Molecular genetics and metabolism reports, 2021-06) Stiles, Ashlee R; Huggins, Erin; Fierro, Luca; Jung, Seung-Hye; Balwani, Manisha; Kishnani, Priya S
    Gaucher disease (GD), a lysosomal storage disorder caused by β-glucocerebrosidase deficiency, results in the accumulation of glucosylceramide and glucosylsphingosine. Glucosylsphingosine has emerged as a sensitive and specific biomarker for GD and treatment response. However, limited information exists on its role in guiding treatment decisions in pre-symptomatic patients identified at birth or due to a positive family history. We present two pediatric patients with GD1 and highlight the utility of glucosylsphingosine monitoring in guiding treatment initiation.