Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders
Tandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of lysosomal storage disorders (LSDs) and how MS/MS has changed the diagnostic rationale in recent years. This fine technology brings more sensitive, specific, and reliable methods than the previous biochemical ones for the analysis of urinary glycosaminoglycans, oligosaccharides, and sialic acid. In sphingolipidoses, the quantification of urinary sphingolipids (globotriaosylceramide, sulfatides) is possible. The measurement of new plasmatic biomarkers such as oxysterols, bile acids, and lysosphingolipids allows the screening of many sphingolipidoses and related disorders (Niemann–Pick type C), replacing tedious biochemical techniques. Applied to amniotic fluid, a more reliable prenatal diagnosis or screening of LSDs is now available for fetuses presenting with antenatal manifestations. Applied to enzyme measurements, it allows high throughput assays for the screening of large populations, even newborn screening. The advent of this new method can modify the diagnostic rationale behind LSDs.
KeywordsLysosomal storage diseases Tandem mass spectrometry Biomarkers
Dried blood spots
Dried urine spots
Enzyme replacement therapy
Flow injection analysis
Glycogen storage disease
Genetic variant of unknown significance
Infantile sialic acid storage disorder
Lysosomal acid lipase deficiency
Lysosomal storage disorders
Analogue 509 of lysosphingomyelin
Multiple reaction monitoring
Multiple of median
Tandem mass spectrometry
Multiple sulfatase deficiency
Nonimmune hydrops fetalis
Niemann-Pick disease type A/B
Niemann–Pick disease type C
Time of flight
Compliance with ethical standards
Conflict of interest
David Cheillan and Séverine Ruet declare they have no conflict of interest.
Christiane Auray-Blais declares she has received reimbursement for attending a symposium from Shire and Sanofi-Genzyme, fees for speaking or organizing education from Shire and Sanofi-Genzyme, funds for research or for a member of staff from Shire, Sanofi-Genzyme and BioMarin Pharmaceuticals, fees for consulting from Amicus Therapeutics, funds for traveling expenses and lectures given from Waters Corp.
Roseline Froissart declares she has received reimbursement for attending a symposium from Sanofi-Genzyme.
Pamela Lavoie declares she has received reimbursement for attending a symposium from Sanofi-Genzyme, BioMarin Pharmaceuticals and Waters Corp, fees for speaking or organizing education from Shire.
Philippe Latour and Cécile Pagan declare they have received reimbursement for attending a symposium and fees for speaking or organizing education from Actelion Pharmaceuticals.
Magali Pettazzoni declares she has received reimbursement for attending a symposium from Shire and BioMarin Pharmaceuticals.
Monique Piraud declares she has received reimbursement for attending a symposium from Shire, Sanofi-Genzyme, and Actelion Pharmaceuticals.
Christine Vianey-Saban declares she has received reimbursement for attending a symposium from Sanofi-Genzyme and BioMarin Pharmaceuticals, and funds for research or for a member of staff from Sanofi-Genzyme.
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