Abstract
Abstract Background: Interest in screening methods for lysosomal storage diseases (LSDs) has increased in recent years, since early diagnosis and treatment are essential to prevent or attenuate the onset of symptoms and the complications of these diseases. In the current work, we evaluated the performance of tandem mass spectrometry (MS/MS) for the detection of some LSDs, aiming the future use of this methodology for the screening of these disorders. Methods: Standard curves and quality control dried blood spots were assayed to evaluate the precision, linearity, and accuracy. A total of 150 controls were grouped according to age and subjected to measurement of lysosomal enzymes deficient in Niemann-Pick A/B, Krabbe, Gaucher, Fabry, Pompe, and Mucopolysaccharidosis type I diseases. Samples from 59 affected patients with a diagnosis of LSDs previously confirmed by fluorimetric methods were analyzed. Results: Data from standard calibration demonstrated good linearity and accuracy and the intra- and interassay precisions varied from 1.17% to 11.60% and 5.39% to 31.24%, respectively. Except for galactocerebrosidase and ?-l-iduronidase, enzyme activities were significantly higher in newborns compared to children and adult controls. Affected patients presented enzymatic activities significantly lower compared to all control participants. Conclusion: Our results show that MS/MS is a promising methodology, suitable for the screening of LSDs, but accurate diagnoses will depend on its correlation with other biochemical and/or molecular analyses.
Highlights
Lysosomal storage diseases (LSDs) comprise a heterogeneous group of more than 50 genetic disorders, which result in the accumulation of macromolecular substrates that would normally be degraded/processed by proteins/enzymes involved in lysosomal metabolism.[1,2] individual lysosomal storage diseases (LSDs) are rare, their combined incidence has been estimated at 1 per 7700 live births.[1]
The present study addresses the implementation of the detection of 6 LSDs by MS/MS (Fabry, Niemann-Pick A/B, Pompe, Gaucher, Krabbe, and Mucopolysaccharidosis type I (MPS-I) diseases) by measuring the activities of a-galactosidase (GLA), acid sphingomyelinase (ASM), a-glucosidase (GAA), b-glucocerebrosidase (ABG), GALC, and a-L-iduronidase (IDUA), respectively, in dried blood spot (DBS) samples from affected and control individuals with different ages
In order to evaluate the precision and accuracy of the technique, quality control materials provided by the Centers for Diseases Control and Prevention (CDC) were assayed
Summary
Lysosomal storage diseases (LSDs) comprise a heterogeneous group of more than 50 genetic disorders, which result in the accumulation of macromolecular substrates that would normally be degraded/processed by proteins/enzymes involved in lysosomal metabolism.[1,2] individual LSDs are rare, their combined incidence has been estimated at 1 per 7700 live births.[1] The progressive accumulation of these molecules leads to cellular dysfunction, which may affect both somatic organs and the central nervous system. Methods: Standard curves and quality control dried blood spots were assayed to evaluate the precision, linearity, and accuracy. Samples from 59 affected patients with a diagnosis of LSDs previously confirmed by fluorimetric methods were analyzed. Affected patients presented enzymatic activities significantly lower compared to all control participants. Conclusion: Our results show that MS/MS is a promising methodology, suitable for the screening of LSDs, but accurate diagnoses will depend on its correlation with other biochemical and/or molecular analyses
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