Oligosaccharide Analysis in Urine by MALDI-TOF Mass Spectrometry for the Diagnosis of Lysosomal Storage Diseases

Abstract

BACKGROUND:There are 45 known genetic diseases that impair the lysosomal degradation of macromolecules. The loss of a single lysosomal hydrolase leads to the accumulation of its undegraded substrates in tissues and increases of related glycoconjugates in urine, some of which can be detected by screening of free oligosaccharides (FOS) in urine. Traditional 1-dimensional TLC for urine oligosaccharide analysis has limited analytical specificity and sensitivity. We developed fast and robust urinary FOS and glycoaminoacid analyses by MALDI-time-of-flight/ time-of-flight (MALDI-TOF/TOF) mass spectrometry for the diagnosis of oligosaccharidoses and other lysosomal storage diseases.

Pitfalls in Diagnosing Neuraminidase Deficiency: Psychosomatics and Normal Sialic Acid Excretion

“…During these years, patient 2 was assessed by multiple specialists and underwent therapy for conversion disorder without success. Her diagnostic history shows that accepting a psychosomatic explanation for neurologic Thin-layer chromatography of urinary oligosaccharides can be labor intensive (van der Ham et al 2007) and difficult to interpret (Xia et al 2013). Measurement of urinary sialic acid levels could be a convenient alternative.…”

Biomarker Characterization by MALDI–TOF/MS

“…The selection of an adequate sample preparation method relies primarily on the chemical characteristics of the targeted analytes. In some cases, biological samples can be directly analyzed without any pretreatment [198][199][200][201][202][203][204][205][206][207][208][209][210][211][212][213]. However, in most cases, simple sample preparation processes are involved, such as liquid-liquid extraction (LLE), solid-phase extraction (SPE), concentration, filtration, desalting, immunoaffinity capturing, and digestion.…”

“…Urine samples were directly analyzed by MALDI-TOF without pretreatment. Characteristic molecular profiles obtained by single-step MALDI-TOF/MS and MS/MS analyses were used for diagnosis of fucosidosis, aspartyl glucosaminuria, GM1 gangliosidosis, Sandhoff disease, α-mannosidosis, sialidosis, and type II and III mucolipidosis [202,203]. MALDI-TOF was also used to evaluate the degree of blood glycation of globins, which is involved in regulating diabetes [204][205][206][207][208][209][210][211][212].…”

Proteomics in Diagnosis: Past, Present and Future

“…As discussed being a cumbersome and time consuming technique 2DE could not reach the clinics, however, Mass spectrometry, especially MALDI-TOF have successfully made its way to pathology labs in the present decade. Several diseases like cancer, Alzheimer's disease, Amyloid lateral sclerosis, renal amyloidosis, and Severe combined immunodeficiency can now be diagnosed using mass spectrometry and its variants [28][29][30][31][32][33][34].…”