@article{UeceylerBikoHoseetal.2016,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Biko, Lydia and Hose, Dorothea and Hoffmann, Lukas and Sommer, Claudia},
  title     = {Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development},
  series = {Molecular Pain},
  volume    = {12},
  journal   = {Molecular Pain},
  number    = {1744806916646370},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147562},
  year      = {2016},
  abstract  = {Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background. Results From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease. Conclusions. Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain.},
  language  = {en}
}
@article{UeceylerSchaeferMackenrodtetal.2016,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Sch{\"a}fer, Kristina A. and Mackenrodt, Daniel and Sommer, Claudia and M{\"u}llges, Wolfgang},
  title     = {High-Resolution Ultrasonography of the Superficial Peroneal Motor and Sural Sensory Nerves May Be a Non-invasive Approach to the Diagnosis of Vasculitic Neuropathy},
  series = {Frontiers in Neurology},
  volume    = {7},
  journal   = {Frontiers in Neurology},
  number    = {48},
  doi       = {10.3389/fneur.2016.00048},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146671},
  year      = {2016},
  abstract  = {High-resolution ultrasonography (HRUS) is an emerging new tool in the investigation of peripheral nerves. We set out to assess the utility of HRUS performed at lower extremity nerves in peripheral neuropathies. Nerves of 26 patients with polyneuropathies of different etiologies and 26 controls were investigated using HRUS. Patients underwent clinical, laboratory, electrophysiological assessment, and a diagnostic sural nerve biopsy as part of the routine work-up. HRUS was performed at the sural, tibial, and the common, superficial, and deep peroneal nerves. The superficial peroneal nerve longitudinal diameter (LD) distinguished best between the groups: patients with immune-mediated neuropathies (n = 13, including six with histology-proven vasculitic neuropathy) had larger LD compared to patients with non-immune-mediated neuropathies (p < 0.05) and to controls (p < 0.001). Among all subgroups, patients with vasculitic neuropathy showed the largest superficial peroneal nerve LD (p < 0.001) and had a larger sural nerve cross-sectional area when compared with disease controls (p < 0.001). Enlargement of the superficial peroneal and sural nerves as detected by HRUS may be a useful additional finding in the differential diagnosis of vasculitic and other immune-mediated neuropathies.},
  language  = {en}
}
@article{UeceylerSchroeterKafkeetal.2016,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Schr{\"o}ter, Nils and Kafke, Waldemar and Kramer, Daniela and Wanner, Christoph and Weidemann, Frank and Sommer, Claudia},
  title     = {Skin Globotriaosylceramide 3 Load Is Increased in Men with Advanced Fabry Disease},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0166484},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178856},
  year      = {2016},
  abstract  = {Background The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity. Methods At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data. Results We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy. Conclusions Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.},
  language  = {en}
}
@article{LendersHennermannKurschatetal.2016,
  author    = {Lenders, Malte and Hennermann, Julia B. and Kurschat, Christine and Rolfs, Arndt and Canaan-K{\"u}hl, Sima and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan and Kampmann, Christoph and Karabul, Nesrin and Giese, Anne-Katrin and Duning, Thomas and Stypmann, J{\"o}rg and Kr{\"a}mer, Johannes and Weidemann, Frank and Brand, Stefan-Martin and Wanner, Christoph and Brand, Eva},
  title     = {Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {11},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {88},
  doi       = {10.1186/s13023-016-0473-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166543},
  year      = {2016},
  abstract  = {Background The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines. Methods Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed. Results Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-na{\"i}ve females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-na{\"i}ve females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were ~8 years younger than females with normal lyso-Gb3 levels. Conclusion The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females.},
  language  = {en}
}