Wien Med Wochenschr (2010) 160/23–24: 600–604 DOI 10.1007/s10354-010-0814-1 Ó Springer-Verlag 2010 Printed in Austria Laboratory and genetic evaluation of Gaucher disease Olaf A. Bodamer and Christina Hung University Childrens Hospital Salzburg and Institute of Inherited Metabolic Diseases, Paracelsus Private Medical University, Salzburg, Austria Received January 25, 2010, accepted June 16, 2010, published online August 16, 2010 Labordiagnostik bei Morbus Gaucher Zusammenfassung. Der Morbus Gaucher (MG) ist eine ver- erbte lysosomale Speicherkrankheit, dem ein Mangel des Enzyms Glukocerebrosidase zugrunde liegt. Die Diagnose eines MG kann aufgrund der entsprechenden klinischen Symptome vermutet und mittels Enzymanalytik in Leukozyten, mononukleären Zel- len, Fibroblasten und Trockenblut auf Filterkarten bestätigt wer- den. Niedrige Enzymaktivitäten sollten unbedingt durch eine molekulargenetische Untersuchung des GBA Genes bestätigt werden. Obwohl es keine weitreichende Genotyp-Phänotyp-Kor- relation gibt, führt das Vorliegen einer p.N370S Mutation auf mindestens einem Allel zu einer nicht-neuronopathischen Ver- laufsform eines MG, während Homozygotie der p.L444P Muta- tion in den meisten Fällen zu einem neuronopathischen MG führt. Die progrediente Speicherung von Glukosylzeramid in mononukleären Zellen und Makrophagen führt zu erhöhten Konzentrationen der Chitotriosidase-Aktivität und von CCL18/ PARC, welche als Biomarker für den Schweregrad des MG als auch das therapeutische Ansprechen verwendet werden können. Bei etwa 6 % der Gaucher-Patienten ist die Chitotriosidase- Aktivität aufgrund einer Nullmutation im Chitotriosidase-Gen nicht nachweisbar. Schlüsselwörter: Glukozerebrosidase, Chitotriosidase, CCL18, Biomarker, Genotyp Summary. Gaucher disease (GD) is an inherited lysosomal storage disorder due to deficiency of glucocerebrosidase. Diag- nosis of GD may be suspected based on clinical symptoms and confirmed by the analysis of glucocerebrosidase in total white cells, mononuclear cells, fibroblasts and dried blood on filter paper. Low enzyme activities should be followed by molecular analysis of the GBA gene. Although there is no obvious genoty- pe–phenotype correlation, the presence of p.N370S protects from neurological involvement whereas homozygosity of p.L444P mostly leads to a neuronopathic form of GD. Progressive storage of glucosylceramide in mononuclear cells and macrophages results in elevated levels of chitotriosidase and CCL18/PARC which may be used as biomarker to assess disease severity and efficacy of treatment. Chitotriosidase activities cannot be ana- lysed in at least 6% of GD patients due to a null mutation in the corresponding gene. Key words: Glucocerebrosidase, chitotriosidase, CCL18, bio- marker, genotype Introduction Gaucher disease (GD; MIM #230800) is an auto- somal recessive inherited lysosomal storage disorder that is due to a deficiency of glucocerebrosidase (acid beta glucosidase; GBA; EC 3.2.1.45) [1]. GBA deficiency results in progressive, intralysosomal accumulation of glucosylceramide in different tissues, primarly in cells of mononuclear origin [1, 2]. Rarely, a variant GD may be secondarily caused by deficiency of the GBA activa- tor saposin C resulting from mutations in the PSAP gene while GBA itself remains functionally intact [3]. Within the subgroups, the clinical phenotype of GD reflects a continuum ranging from neuronopathic forms (GD types II and III) to the more frequent visceral form (GD type I) and from early onset to late onset within subgroups. Details on the clinical phenotype have been reviewed extensively in the medical litera- ture and may be found in this issue of the Wiener Medizinische Wochenschrift [1]. Diagnosis of GD may be suspected based on the presence of characteristic clinical symptoms but the differential diagnosis may still include different lyso- somal storage disorders such as Niemann Pick Disease A/B [4]. A thorough medical history, pedigree analysis, clinical examination and radiologic investigations are important prerequisites prior to biochemical evalua- tion of a patient for the presence of GD. Biochemical and genetic evaluation for GD should be done only by a Correspondence: Olaf Bodamer, M.D., Institute of Inherited Metabol- ic Diseases, Paracelsus Private Medical University Salzburg, Struber- gasse 21, 5020 Salzburg, Austria. Fax: þþ43-662-4482-2604, E-mail: olaf.bodamer@pmu.ac.at themenschwerpunkt 600 Ó Springer-Verlag 23–24/2010 wmw