title: Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1 under enzyme replacement therapy: a prospective study.
abstract: BACKGROUND
  Dyslipidemia in Gaucher disease includes reduced total, low-density lipoprotein (LDL)-, and high-density lipoprotein (HDL)-cholesterol (C). No prospective analysis of lipid profile changes in treatment-naïve patients under enzyme replacement therapy (ERT) is available.
  
  
  METHODS
  We analyzed lipid profile changes during ERT in a prospective controlled manner. Twelve treatment-naïve patients, Gaucher disease type 1 (GD1), 29.5 ± 12.9 years, 4M/8F. Diagnosis was made by enzymatic measurement and mutational analysis. Total-, LDL-, and HDL-C, triglycerides (TG), and LDL subfractions were assessed before the start of ERT with imiglucerase and biannually for 3 years. Patients were matched with healthy controls before and after 3 years of ERT.
  
  
  RESULTS
  At baseline, we found severely reduced HDL-C concentrations (23.6 ± 5.4 mg/dl) and enhanced LDL/HDL ratios (3.1 ± 0.7). HDL-C increased after 6 months (29.2 ± 5.7, p = 0.023), LDL/HDL ratio decreased after 30 months (2.5 ± 0.5, p = 0.039). TG, even not consistently enhanced at baseline (128 ± 31.3 mg/dl), yet higher than in controls (p < 0.001), decreased after 18 months, being comparable with controls after 3 years of ERT. Small, dense LDL (mg/dl) increased continuously without significant difference to controls. After 3 years of ERT, only reduced HDL-C concentrations persisted as a potentially atherogenic alteration; however, mean concentrations markedly improved (42.9 ± 8.3 mg/dl, p < 0.001). Lipid parameters correlated with six markers of disease severity.
  
  
  CONCLUSIONS
  This is the first prospective controlled study regarding lipid profile dynamics during ERT (glucocerebrosidase) in initially treatment-naïve GD1 patients. The most important changes were reduced HDL-C and enhanced LDL/HDL ratio. Their dynamics during ERT and correlations with markers of disease activity suggest that they can be considered markers of disease severity and follow-up in Gaucher patients under treatment.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, 1st Clinic of Internal Medicine, Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany, zimmeran@uni-mainz.de.
authors.forename: Anca
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Paula
authors.initials: P
authors.lastname: Grigorescu-Sido
authors.forename: Heidi
authors.initials: H
authors.lastname: Rossmann
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.forename: Cristina
authors.initials: C
authors.lastname: Drugan
authors.forename: Camelia
authors.initials: C
authors.lastname: Al Khzouz
authors.forename: Simona
authors.initials: S
authors.lastname: Bucerzan
authors.forename: Ioana
authors.initials: I
authors.lastname: Naşcu
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Daniel
authors.initials: D
authors.lastname: Leucuţa
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D000328:Adult; D056947:Enzyme Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012383:Romania / Q000453:epidemiology; D055815:Young Adult
chemical_list: D008055:Lipids; D005962:Glucosylceramidase; C090568:imiglucerase