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Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment

Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous a...

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Autores principales: Mhanni, Aizeddin, Boutin, Michel, Stockl, Frank, Johnston, Janine, Barnes, Jeff, Duerksen, Donald, Zimmer, Leanne, Auray-Blais, Christiane, Rockman-Greenberg, Cheryl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168891/
https://www.ncbi.nlm.nih.gov/pubmed/31991859
http://dx.doi.org/10.3390/diagnostics10020069
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author Mhanni, Aizeddin
Boutin, Michel
Stockl, Frank
Johnston, Janine
Barnes, Jeff
Duerksen, Donald
Zimmer, Leanne
Auray-Blais, Christiane
Rockman-Greenberg, Cheryl
author_facet Mhanni, Aizeddin
Boutin, Michel
Stockl, Frank
Johnston, Janine
Barnes, Jeff
Duerksen, Donald
Zimmer, Leanne
Auray-Blais, Christiane
Rockman-Greenberg, Cheryl
author_sort Mhanni, Aizeddin
collection PubMed
description Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood–retinal and blood–brain barriers for patients with GD and other neuropathic lysosomal storage disorders.
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spelling pubmed-71688912020-04-20 Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment Mhanni, Aizeddin Boutin, Michel Stockl, Frank Johnston, Janine Barnes, Jeff Duerksen, Donald Zimmer, Leanne Auray-Blais, Christiane Rockman-Greenberg, Cheryl Diagnostics (Basel) Article Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood–retinal and blood–brain barriers for patients with GD and other neuropathic lysosomal storage disorders. MDPI 2020-01-26 /pmc/articles/PMC7168891/ /pubmed/31991859 http://dx.doi.org/10.3390/diagnostics10020069 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mhanni, Aizeddin
Boutin, Michel
Stockl, Frank
Johnston, Janine
Barnes, Jeff
Duerksen, Donald
Zimmer, Leanne
Auray-Blais, Christiane
Rockman-Greenberg, Cheryl
Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment
title Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment
title_full Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment
title_fullStr Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment
title_full_unstemmed Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment
title_short Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment
title_sort mass spectrometry evaluation of biomarkers in the vitreous fluid in gaucher disease type 3 with disease progression despite long-term treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168891/
https://www.ncbi.nlm.nih.gov/pubmed/31991859
http://dx.doi.org/10.3390/diagnostics10020069
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