Detecting lysosomal storage disorders by glycomic profiling using liquid chromatography mass spectrometry

Area of Science:

• Biochemistry
• Analytical Chemistry
• Clinical Diagnostics

Background:

• Current lysosomal storage disorder (LSD) testing using liquid chromatography-mass spectrometry (LC-MS) requires multiple methods.
• Detecting abnormal accumulation of oligosaccharides, mucopolysaccharides, and glycolipids is complex.
• There is a need for improved clinical testing efficiency for LSDs.

Purpose of the Study:

• To develop a single LC-MS method for simultaneous identification of LSDs.
• To improve clinical testing efficiency with minimal sample preparation.
• To enable rapid diagnosis and support further investigations for LSDs.

Main Methods:

• A single chromatographic method was developed using an amide column and high pH conditions.
• Glycomic profiling was performed using LC ion-mobility high-resolution MS for biomarker discovery.
• Targeted LC-MS/MS analyses were conducted on urine, serum, and dried blood spot samples for clinical validation.

Main Results:

• Untargeted glycomic profiling identified 20 biomarkers for mucopolysaccharidoses subtyping.
• A rapid test was developed to identify at least 27 LSDs, including oligosaccharidoses, mucopolysaccharidoses, and sphingolipidoses.
• The method achieved 88% correct disease subtyping in 115 urine samples and reliably detected Gaucher disease biomarkers in dried blood spots.

Conclusions:

• Glycomic profiling by LC-MS is effective for identifying a range of LSDs.
• This test can expedite clinical evaluations and aid in diagnosis.
• The method supports and clarifies results from gene sequencing and enzyme studies.