Multiplex detection method for diagnosing and follow-up of Lysosomal Storage Disorders
A new and innovative diagnostic method using multiplex LC-MS/MS on dried blood spots (DBS) has been developed and validated for three common Lysosomal Storage Disorders: Gaucher, Fabry, and Niemann-Pick types A, A/B, and B. This approach simultaneously measures three disease-specific biomarkers: GlcSph, Lyso-Gb3, and Lyso-SM, all within in a single DBS sample. It provides a sensitive, reliable, and cost-effective way to support early diagnosis, monitor disease progression, and evaluate treatment effectiveness.
Situation before
Gaucher disease (GD), Fabry disease (FD), and Niemann-Pick types A/AB/B, also know as acid sphingomyelinase deficiency (ASMD), are three of the most common treatable lysosomal storage disorders (LSDs). Each is caused by a deficiency in a specific enzyme, leading to the accumulation of disease-related lipids in the body and a broad spectrum of clinical symptoms. These clinical symptoms are often nonspecific and can mimic other conditions, making early diagnosis challenging. As a result, many patients are not diagnosed until adulthood, by which time irreversible organ damage may have already occurred, significantly increasing the burden of disease and limiting treatment outcomes.
The traditional diagnostic approach for Gaucher, Fabry and ASMD diseases involves enzyme activity testing, followed by genetic testing if the enzyme levels are abnormal. However, these methods have their limitations. Both tests might be inconclusive and lead to interpretation difficulties. Furthermore, they do not provide information about disease severity or progression, making these results less useful for monitoring treatment response or tracking disease progression over time.
Recent research into lysosomal biomarkers has shown promising results in improving the diagnostic process. Biomarkers such as glucosylsphingosine (GlcSph), globotriaosylsphingosine (Lyso-Gb3) and Lyso-Sphingomyeline (Lyso-SM) are specific to Gaucher, Fabry and ASMD diseases, respectively. These biomarkershave been found to correlate with disease presence, disease severity and treatment response. When measured in blood or other biological fluids, biomarkers can serve as more reliable and more stable indicators of disease presence and progression than enzyme activity tests alone. However, even though biomarkers hold great potential, their widespread use in clinical practice is still limited due to the lack of universal reference ranges for these biomarkers and standardised and validated testing methods.
Technology
The University of Antwerp and Antwerp University Hospital have developed a multiplex liquid chromatography-tandem mass spectrometry (LC-MS/MS) method on Dried Blood Spots (DBS) for Gaucher disease, Fabry disease and ASMD which enables the simultaneous detection of three biomarkers: GlcSph, Lyso-Gb3 and Lyso-SM.
This innovative diagnostic technology offers several significant advantages that position it as a superior approach for diagnosing and follow-up of Lysosomal Storage Disorders (Gaucher, Fabry, and Niemann-Pick A/AB/B):
- Validated methodology: The developed method was validated according to the international Clinical and Laboratory Standards Institute (CLSI) guidelines, ensuring the highest standards for precision, accuracy, and reproducibility.
- Comprehensive reference ranges: The largest cohort to date, comprising 1,480 healthy individuals with confirmed normal enzyme activity, was used to establish age- and gender-specific reference ranges for GlcSph and Lyso-Gb3. Reference range determination for Lyso-SM is currently underway using the same number of samples with normal enzyme activity.
- Diagnostic value: As the biomarkers are highly specific to their respective diseases, and their levels in blood correlate with disease severity, they offer clear advantages over the traditional enzyme activity assays and genetic testing, especially in patients with mild or atypical symptoms, or when enzyme activity does not accurately reflect disease status.
- Practical sampling approach: Dried blood spots (DBS) further enhance this approach, as they are minimally invasive, easy to collect, transport, and store, and require significantly less sample volume compared to other biological samples like plasma or serum. These features make DBS an ideal medium for large-scale screening and diagnostic programs.
Partners we search for
We are looking for:
- Diagnostic assay manufacturers interested in adding or integrating this technology in their product portfolio
- Diagnostic laboratories/healthcare institutions interested in extending or enhancing their diagnostic offerings
- Pharmaceutical and Biotechnology companies interested in improved patient identification, disease severity classification and monitoring of treatment outcomes in their clinical trials
About the researchers/research group
The technology has been developed by the University of Antwerp (Laboratory of Experimental Medicine and Pediatrics - LEMP) and the University Hospital of Antwerp (Department of Pediatrics). Dr. Amber Van Baelen is a medical doctor with special interest in Lysosomal Storage Disorders and an expert in LC-MS/MS detection of Lyso-biomarkers across various biological samples, particularly dried blood spots (DBS). She was supported by Prof. Dr. François Eyskens, a leading authority in metabolic disorders and newborn screening, with decades of experience in clinical research, patient care, and therapeutic advancements. Additionally, Prof. Dr. Stijn Verhulst contributed his extensive expertise in clinical research and pediatric care.
IP position
The technology is patent-pending (WO2023232942) and has been published in Molecular Genetics and Metabolism Reports. Reference: Van Baelen A, Roosens L, Devos S, Verhulst S, Eyskens F. A new multiplex analysis of glucosylsphingosine and globotriaosylsphingosine in dried blood spots by tandem mass spectrometry. Mol Genet Metab Rep. 2023 Aug 18;37:100993. doi: 10.1016/j.ymgmr.2023.100993. PMID: 37649874; PMCID: PMC10462886.
More information
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