Review and Proposal of Alternative Technologies for Comprehensive and Reliable Newborn Screening Using Paper Borne Urine Samples for Lysosomal Storage Disorders: Glycosphingolipid Disorders

Abstract

Few current methods are efficient to detect a high number of lysosomal storage disorders (LSDs) in newborn screening. Therefore, we propose a stepwise procedure that starts with the use of paper borne urine samples (Berry-Woolf specimen) for the inexpensive detection of elevated lysosomal content and the identification of which of the three majors biochemical groupsmucopolysaccharides, oligosaccharides, and glycosphingolipids -is detected. Urine samples are preferable to blood samples because of their higher concentrations of the relevant analytes. Subsequent steps would precisely determine which enzyme deficiency is involved. As a summary, following our previous papers on the detection of elevated oligosaccharides and mucopolysaccharides, here we describe how elevated urinary glycosphingolipids (GSLs) could be fluorometrically detected using the reagent 5-hydroxy-1-tetralone (HOT) and subsequently identified with precision by continuous thin layer chromatography or other techniques. We also outline the steps required for the validation of this procedure for its introduction in newborn screening programs.

Four Decades of Newborn Screening: A Historical Perspective of Laboratory Practices

“…The inspiration came to me thinking about the visit I made to the Laboratory of Metabolopathies in mid-February, in which he informed me that they had advanced the sampling from 3 days to 24 hours of life of the newborn, with therefore, the assay of reducers in dried urine on adsorbent paper, with Mandelin's reagent, which we introduced in 1978 [1][2][3][4][5][6][7], for the detection of galactosemia and other inborn errors of carbohydrate metabolism, was unfeasible for them due to the high number of positive results, which required them to perform numerous cTLC of sugars with our procedure. They arranged to determine total galactose in blotter-dried blood with a procedure approach marketed by a company we took to the NBS field in 1985.…”

“…Urine also facilitates the work to detect lysosomal disorders since the biochemical markers are excreted in higher concentrations than what is in the blood, separated into three groups: mucopolysaccharidosis (MPS), oligosaccharidosis, and glycosphingolipidoses [15][16][17][18]; the positive ones are subjected to cTLC or another method, to get closer to identifying markers or marker of the specific pathology, gradually; it is what analytical chemists call analytical gait, these works are commented [19] and are the origin of 'Project Find' for the early and accurate diagnosis of MPS [20], (biochemical markers in dried urine are more stable than enzymes in dried blood. This is a significant advantage).…”

“…The procedures we developed and applied using the Berry-Woolf specimen [18] do not require special knowledge or expensive instrumentation. The results are easy to interpret and intuitive (consult monographs at the end).…”