Biomarkers for lysosomal storage disorders: identification and application as exemplified by chitotriosidase in Gaucher disease.
A biomarker is an analyte that indicates the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. An ideal biomarker provides indirect but ongoing determinations of disease activity. In the case of lysosomal storage disorders (LSDs), metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Potential clinical applications of biomarkers are found in improved diagnosis, monitoring of disease progression and assessment of therapeutic correction. These applications are illustrated by reviewing the use of plasma chitotriosidase in the clinical management of patients with Gaucher disease, the most common LSD. The ongoing debate on the value of biomarkers in patient management is addressed. Novel analytical methods have revolutionized the identification and measurement of biomarkers at the protein and metabolite level. Recent developments in biomarker discovery by proteomics are described and the future for biomarkers of LSDs is discussed.


CONCLUSIONS
Besides direct applications for biomarkers in patient management, biomarker searches are likely to render new insights into pathophysiological mechanisms and metabolic adaptations, and may provide new targets for therapeutic intervention.
Aerts
Johannes M
JM
Clinical Proteomics Facility, Academic Medical Center, Amsterdam, The Netherlands. j.m.aerts@amc.uva.nl
van Breemen
Marielle J
MJ
Bussink
Anton P
AP
Ghauharali
Karen
K
Sprenger
Richard
R
Boot
Rolf G
RG
Groener
Johanna E
JE
Hollak
Carla E
CE
Maas
Mario
M
Smit
Suzanne
S
Hoefsloot
Huub C
HC
Smilde
Age K
AK
Vissers
Johannes Pc
JP
de Jong
Sheryas
S
Speijer
Dave
D
de Koster
Chris G
CG
D015415:Biomarkers / Q000097:blood; D005776:Gaucher Disease / Q000175:diagnosis*; D005962:Glucosylceramidase; D006596:Hexosaminidases / Q000097:blood*; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000175:diagnosis*; D008264:Macrophages / Q000502:physiology; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D001617:beta-Glucosidase / Q000502:physiology
D015415:Biomarkers; D006596:Hexosaminidases; C086400:chitotriosidase; D001617:beta-Glucosidase; C517537:GBA2 protein, human; D005962:Glucosylceramidase