caa a22 4500 467933820 CHVBK 20180406152951.0 cr unu---uuuuu 170328e20061001xx s 000 0 eng 10.1007/s10545-006-0363-3 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0363-3 Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C [Elektronische Daten] [Markus Ries, Ellen Schaefer, Till Lührs, Latha Mani, Jana Kuhn, Marie Vanier, Frank Krummenauer, Andreas Gal, Michael Beck, Eugen Mengel] Summary: Laboratory diagnosis of lysosomal storage disorders, especially sphingomyelinase deficiency (Niemann-Pick disease type A/B) and Niemann-Pick disease type C (NPC) can be challenging. We therefore aimed to analyse the feasibility of first-step screening with specific chitotriosidase cut-off values in children ≤ 10 years of age with visceral organomegaly (hepatomegaly, splenomegaly, or hepatosplenomegaly) in whom a storage disorder was suspected. We conducted a retrospective, cross-sectional, referral, single-centre study to assess diagnostic test properties in 106 individuals. Median chitotriosidase activity was 12 655 nmol/h per ml (interquartile range 4693-20982) in Gaucher disease (GD); 780 (465-1298) in SMD (sphingomyelinase deficiency); 925 (319-1215) in NPC and 50 (29-54) in patients with miscellaneous diseases. To restrict the differential diagnosis to GD, SMD or NPC, chitotriosidase activity above 200 nmol/h per ml had a sensitivity of 96%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 95%. For GD alone, chitotriosidase activity above 4000 nmol/h per ml had a sensitivity of 77%, specificity of 100%, PPV of 100% and NPV of 92%. Of the 44 patients analysed, 4.5% were homozygous and 36.4% heterozygous for chitotriosidase gene duplication. Adjusting for the chitotriosidase genotype, chitotriosidase activities were higher in GD type III than in GD type I. We conclude that, in the above setting, the degree of elevation of chitotriosidase activity can be applied to increase the likelihood of GD, SMD, or NPC and guide the choice of the appropriate confirmatory assay. SSIEM and Springer, 2006 Ries Markus Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut Schaefer Ellen Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany aut Lührs Till Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut Mani Latha Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut Kuhn Jana Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut Vanier Marie Laboratoire Fondation Gillet-Mérieux, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France aut Krummenauer Frank Clinical Epidemiology and Health Economy Unit, Dresden University of Technology, Dresden, Germany aut Gal Andreas Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany aut Beck Michael Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut Mengel Eugen Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/5(2006-10-01), 647-652 0141-8955 29:5<647 2006 29 10545 https://doi.org/10.1007/s10545-006-0363-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0363-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ries Markus Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut NATIONALLICENCE 700 1- Schaefer Ellen Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany aut NATIONALLICENCE 700 1- Lührs Till Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut NATIONALLICENCE 700 1- Mani Latha Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut NATIONALLICENCE 700 1- Kuhn Jana Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut NATIONALLICENCE 700 1- Vanier Marie Laboratoire Fondation Gillet-Mérieux, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France aut NATIONALLICENCE 700 1- Krummenauer Frank Clinical Epidemiology and Health Economy Unit, Dresden University of Technology, Dresden, Germany aut NATIONALLICENCE 700 1- Gal Andreas Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany aut NATIONALLICENCE 700 1- Beck Michael Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut NATIONALLICENCE 700 1- Mengel Eugen Center for Lysosomal Storage Disorders, Children's Hospital, University of Mainz, Mainz, Germany aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/5(2006-10-01), 647-652 0141-8955 29:5<647 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer