Kurzfassung

Background
Gaucher Disease (GD) is a rare autosomal recessive hereditary disorder of
glycosphingolipid metabolism, characterized by the accumulation of glucosylceramide in
cells of the reticulo-endothelial system, due to deficient activity of the lysosomal enzyme,
beta-glucosidase (glucocerebrosidase, EC 3.2.1 .45). The clinical picture is different ·
according to the three types of Gaucher disease: type 1 can manifest at any age and lacks
neurological symptoms, whereas type 2 and type 3 are...Background
Gaucher Disease (GD) is a rare autosomal recessive hereditary disorder of
glycosphingolipid metabolism, characterized by the accumulation of glucosylceramide in
cells of the reticulo-endothelial system, due to deficient activity of the lysosomal enzyme,
beta-glucosidase (glucocerebrosidase, EC 3.2.1 .45). The clinical picture is different ·
according to the three types of Gaucher disease: type 1 can manifest at any age and lacks
neurological symptoms, whereas type 2 and type 3 are characterized by the presence of
neurological involvement
Gaucher disease type 1 is the most frequent form and presents with a broad spectrum of
clinical manifestations varying in severity, age of manifestation, rate of progression and
organs affected. Common manifestations are anaemia, thrombocytopenia, hepatosplenomegaly
and bone disease. The skeletal manifestations of GD, which may lead to
significant pain, disability and a progressive reduction in quality of life include abnormal
bone remodelling, osteopenia, osteoporosis, lytic lesions, avascular necrosis, pathological
fractures and vertebral collapse.
Skeletal response to treatment is variable in GD on an individual basis and the
pathophysiology of bone disease in Gaucher patients is not completely understood.
Signaling networks between osteoclasts and osteoblasts are central to the regulation of
bone turnover. A previous review of the current literature investigating bone disease and
bone markers in Gaucher disease type 1 yields insufficient evidence for characterization
of bone disease in terms of predictive markers and concludes that a greater
understanding of bone markers and their relation to bone manifestations of GD is
required. Various SNPs have been related to variations in bone mineral density. Previous
unpublished work of our group showed in a pilot study a relation of bone mineral density in
patients with M. Gaucher to the Fokl polymorphism in the gene of the vitamin D receptor.
Further SNPs with impact on BMD and osteoporotic fracture risk had been described:
vitamin D receptor (VDR), estrogen a receptor (ERa), collagen type 1 a1 gene (COL1A1), calcitonin receptor (CTR), osteoprotegerin (OPG).
We aim to assess clinical outcome under ERT and investigate dynamic changes of bone
disease in patients with GD type 1 under ERT by assessment of BMD and bone markers
in relation to: SNPs with impact on bone mass, clinical variables, parameters of disease
severity, parameters of lipid and carbohydrate metabolism, of subclinical inflammation and,
adipokine profile. Furthermore, we aim to investigate bone disease and predictive
biomarkers after appropriate substitution in vitamin D deficient patients and under
antiresorptive treatment with bisphosphonates if osteoporosis is present (according to
current guidelines in treatment of osteoporosis).

 » weiterlesen» einklappen