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Lysosomal diseases: diagnostic update

  • ICIEM Symposium 2013
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Technological developments in newborn and population screening, biomarker discovery for monitoring treatment and rapid high throughput DNA sequencing are having a great impact on the diagnostic procedure for symptomatic patients with lysosomal storage diseases. The use of dried blood spots, initially for newborn screening, has stimulated the introduction of automated, rapid and more sensitive methods for the assay of lysosomal enzymes, including the synthesis of novel substrates. Storage products and secondary metabolites in urine and cells can be identified and measured very accurately and sensitively by high performance liquid chromatography and tandem mass spectrometry. This has enhanced the preliminary metabolite screen for LSDs and facilitated the diagnosis of transport defects. Fast, reliable and affordable high throughput DNA sequencing, such as whole or selected exome sequencing, is helping to make diagnoses in difficult cases, to reveal novel gene defects, to widen the clinical spectrum of diseases and possibly to identify modifying genetic factors. Bioinformatics will be necessary to handle the data generated by these new technologies. Notwithstanding, these technical innovations, accurate and reliable diagnosis will still depend on the knowledge and experience of skilled laboratory staff.

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Acknowledgments

I would like to acknowledge the collaboration and friendship of my colleagues in the LSD Diagnostic Laboratory at Great Ormond Street Hospital, London, with whom I worked for many years and without whom this talk could not have been given. In particular, I would like to thank Clare Beesley (Molecular Genetics), Kevin Mills (Mass Spectrometry) and Liz Young (Enzymology), all at University College London Institute of Child Health and Graham Hamilton (Bioinformatics, Glasgow University Polyomics) for sharing their knowledge with me.

Conflicts of interest

Bryan Winchester has received research grants, consulting fees or honoraria, payment for lectures or support for travel to meetings from Actelion, Biomarin, Genzyme and Shire TKT.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by the author.

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  1. Biochemistry Research Group, UCL Institute of Child Health at Great Ormond Street Hospital, University College London, London, UK

    Bryan Winchester

  2. British MPS Society, Amersham, UK

    Bryan Winchester

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Correspondence to Bryan Winchester.

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Communicated by: Douglas A. Brooks

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Winchester, B. Lysosomal diseases: diagnostic update. J Inherit Metab Dis 37, 599–608 (2014). https://doi.org/10.1007/s10545-014-9710-y

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