Glucosylsphingosine (Lyso-Gb₁): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.

Gayed, Matthew M

Jung, Seung-Hye

Huggins, Erin

Rodriguez-Rassi, Eleanor

DeArmey, Stephanie

Kishnani, Priya Sunil

Stiles, Ashlee R

2023-01-03T15:56:49Z

2023-01-03T15:56:49Z

2022-11

2023-01-03T15:56:47Z

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.

ijms232314938

1422-0067

1422-0067

https://hdl.handle.net/10161/26419

eng

MDPI AG

International journal of molecular sciences

10.3390/ijms232314938

Humans

Gaucher Disease

Psychosine

Enzyme Replacement Therapy

Biomarkers

Glucosylsphingosine (Lyso-Gb₁): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.

Journal article

Huggins, Erin|0000-0002-7594-4511

Kishnani, Priya Sunil|0000-0001-8251-909X

14938

23

Duke

School of Medicine

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Molecular Genetics and Microbiology

Pediatrics

Pediatrics, Medical Genetics

Duke Clinical Research Institute

Institutes and Provost's Academic Units

Initiatives

Duke Innovation & Entrepreneurship

Published

23