title: Impact of imiglucerase on the serum glycosylated-ferritin level in Gaucher disease.
abstract: Gaucher disease (GD) is a lysosomal storage disorder, caused by deficient activity of the enzyme glucocerebrosidase, which can be treated by enzyme-replacement therapy (ERT). No prognostic marker can predict long-term complications of GD but several markers are used in therapeutic monitoring: chitotriosidase, total serum ferritin (TSF), angiotensin-converting enzyme (ACE) and tartrate-resistant acid phosphatase (TRAP). They all increase with disease progression and generally decrease under ERT. This study was undertaken to investigate ferritin glycoforms, i.e., glycosylated ferritin (GF) and non-glycosylated ferritin (NGF) concentrations, as potential markers for the follow-up of GD therapy. GF and NGF determinations for GD patients followed in a single center between 1996 and 2007 were analyzed using two approaches: (1) the serum levels of 12 untreated patients were compared with those of 10 patients after 48 months on ERT; (2) the evolution of serum levels under ERT in 15 patients were analyzed using linear/logarithmic mixed models. TSF and NGF levels did not differed significantly between untreated patients and those on ERT (TSF: 524.5 (range 221.0-2045.0) μg/L vs. 410.5 (range 115.0-1587.0) μg/L, respectively, p=0.72; NGF: 340.0 (range 182.8-1717.8) μg/L vs. 199.9 (range 77.1-649.8) μg/L, p=0.09). The percent GF was significantly lower in untreated patients than in those on ERT (27.0% (range 8.0-51.0) vs. 43.5% (range 22.0-80.0) respectively; p=0.02). The percent GF increased significantly during ERT (slope=0.156% [95% confidence interval (CI), 0.03; 0.29] per month, p=0.01) regardless of whether NGF and TSF significantly decreased during ERT (slope=-1.4% per month [95%CI, -1.9%; -1.0%], p<0.0001; slope=-1.1% [95%CI, -1.6%; -0.6%] per month, p<0.0007, respectively). Thus, GF is low in untreated GD patients. GF and NGF changed significantly under ERT and might be of clinical value for GD management under treatment.
authors.affiliation: Médicine Interne, Hôpital Jean-Verdier, Assistance Publique-Hôpitaux de Paris, Université Paris XIII, Referral Center for Lysosomal Diseases, Avenue du 14 juillet, 93140 Bondy, France. jerome.stirnemann@jvr.aphp.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Stirnemann
authors.forename: Anne
authors.initials: A
authors.lastname: Boutten
authors.forename: Corine
authors.initials: C
authors.lastname: Vincent
authors.forename: Arsene
authors.initials: A
authors.lastname: Mekinian
authors.forename: Djazia
authors.initials: D
authors.lastname: Heraoui
authors.forename: Bruno
authors.initials: B
authors.lastname: Fantin
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
authors.forename: France
authors.initials: F
authors.lastname: Mentré
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D056947:Enzyme Replacement Therapy; D005260:Female; D005293:Ferritins / Q000097:blood*; D005776:Gaucher Disease / Q000097:blood* / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D006023:Glycoproteins
chemical_list: D005293:Ferritins; D005962:Glucosylceramidase; C051036:glycosylated ferritin; D006023:Glycoproteins; C090568:imiglucerase