Changes in the atherogenic profile of patients with type 1 Gaucher disease after miglustat therapy

  • J. Puzo
    Biochemistry Department, San Jorge Hospital, Huesca, Spain
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  • P. Alfonso
    Centre for Biomedical Network Research on Rare Disease (CIBERER), Spain

    Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain
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  • P. Irun
    Centre for Biomedical Network Research on Rare Disease (CIBERER), Spain

    Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain
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  • J. Gervas
    Centre for Biomedical Network Research on Rare Disease (CIBERER), Spain

    Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain
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  • M. Pocovi
    Centre for Biomedical Network Research on Rare Disease (CIBERER), Spain

    Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain

    Department of Biochemistry, Molecular and Cellular Biology, University of Zaragoza, Zaragoza, Spain
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  • P. Giraldo
    Corresponding author at: Pilar Giraldo, S° Hematología, Hospital Universitario Miguel Servet, P° Isabel La Católica 1–3, 50006 Zaragoza, Spain. Tel.: +34 670 285 339; fax: +34 976 468 041.
    Centre for Biomedical Network Research on Rare Disease (CIBERER), Spain

    Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain

    Hematology Department, Miguel Servet University Hospital, Zaragoza, Spain
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      Type 1 Gaucher disease (GD1) is an autosomal recessive lysosomal storage disorder associated with abnormal accumulation of glucocerebrosides. Plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) are decreased in GD1 patients. The effects of substrate reduction therapy (SRT) with miglustat on plasma lipids and atherogenic factors have not yet been examined. Here, we report plasma atherogenic profile data from GD1 patients undergoing long-term SRT.


      Plasma was analysed in 26 GD1 patients treated with miglustat for up to 36 months. Ten patients were therapy-naïve and 16 had switched from enzyme replacement therapy (ERT); the interval between stopping ERT and starting SRT was 2–6 weeks. Plasma TC, triglycerides (TG), LDL-c, HDL-c, apolipoproteins (apoA-I, apoB, and Lp[a]), C-reactive protein (CRP) concentrations, and chitotriosidase activity were measured before SRT (baseline) and at 12, 24, and 36 months follow up.


      In therapy-naïve patients, miglustat significantly increased plasma HDL-c and apoA-I, and slightly increased TC; while TG, CRP concentrations, and TC/HDL-c ratios decreased significantly after 24 months. In contrast, there were no changes in HDL-c and apoA-I, or in the TC/HDL-c ratio in switch patients. However, a decrease in CRP was observed after 12 months. LDL-c and apoB were not significantly altered in either patient group.


      Miglustat appears to have beneficial effects on plasma lipid, lipoprotein, and CRP concentrations in therapy-naïve GD1 patients, resulting in an improved atherogenic lipid profile. Further studies are required to determine the effect of miglustat on coronary heart disease risk.


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