Journal of Inherited Metabolic Disease

, Volume 41, Issue 3, pp 457–477 | Cite as

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

  • Monique Piraud
  • Magali Pettazzoni
  • Pamela Lavoie
  • Séverine Ruet
  • Cécile Pagan
  • David Cheillan
  • Philippe Latour
  • Christine Vianey-Saban
  • Christiane Auray-Blais
  • Roseline Froissart


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.


Lysosomal storage diseases Tandem mass spectrometry Biomarkers 



Amniotic fluid


Arylsulfatase A




Ceroid lipofuscinosis


Chondroitin sulfate


Dried blood spots


1,9-Dimethylmethylene blue


Dried urine spots


Dermatan sulfate


Enzyme replacement therapy


Fabry disease


Flow injection analysis






Gaucher disease




Glycogen storage disease


Genetic variant of unknown significance


Heparan sulfate


Internal standard


Infantile sialic acid storage disorder


Krabbe disease


Keratan sulfate


Lysosomal acid lipase deficiency


Liquid chromatography


Liquid–liquid extraction


Lysosomal storage disorders














Analogue 509 of lysosphingomyelin


Metachromatic leukodystrophy




Multiple reaction monitoring


Multiple of median


Tandem mass spectrometry


Multiple sulfatase deficiency


Newborn screening


Nonimmune hydrops fetalis


Niemann–Pick disease


Niemann-Pick disease type A/B


Niemann–Pick disease type C




Pompe disease




Retention time






Solid-phase extraction


Thin-layer chromatography


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.

Supplementary material

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10545_2017_126_MOESM2_ESM.doc (130 kb)
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10545_2017_126_MOESM3_ESM.doc (264 kb)
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Copyright information

© SSIEM 2018

Authors and Affiliations

  • Monique Piraud
    • 1
  • Magali Pettazzoni
    • 1
  • Pamela Lavoie
    • 2
  • Séverine Ruet
    • 1
  • Cécile Pagan
    • 1
  • David Cheillan
    • 1
  • Philippe Latour
    • 3
  • Christine Vianey-Saban
    • 1
  • Christiane Auray-Blais
    • 2
  • Roseline Froissart
    • 1
  1. 1.Unité Maladies Héréditaires du Métabolisme, Service de Biochimie et Biologie Moléculaire Grand Est, Centre de Biologie et de Pathologie EstHospices Civils de LyonBron cedexFrance
  2. 2.Service de Génétique Médicale, Département de Pédiatrie, Faculté de médecine et des sciences de la santéUniversité de SherbrookeSherbrookeCanada
  3. 3.Unité de Neurogénétique Moléculaire, Service de Biochimie et Biologie Moléculaire Grand Est, Centre de Biologie et de Pathologie EstHospices Civils de LyonLyonFrance

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