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- Weinreb, Neal J, et al.
(författare)
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Gaucher disease type 1 : revised recommendations on evaluations and monitoring for adult patients.
- 2004
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Ingår i: Semin Hematol. - 0037-1963. ; 41:4 Suppl 5, s. 15-22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- For patients with type 1 Gaucher disease, challenges to patient care posed by clinical heterogeneity, variable progression rates, and potential permanent disability that can result from untreated or suboptimally treated hematologic, skeletal, and visceral organ involvement dictate a need for comprehensive, serial monitoring. An updated consensus on minimum recommendations for effective monitoring of all adult patients with type 1 Gaucher disease has been developed by the International Collaborative Gaucher Group (ICGG) Registry coordinators. These recommendations provide a schedule for comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects of this disease. The initial assessment should include confirmation of deficiency of beta-glucocerebrosidase, genotyping, and a complete family medical history. Other assessments to be performed initially and at regular intervals include a complete physical examination, patient-reported quality of life using the SF-36 survey, and assessment of hematologic (hemoglobin and platelet count), visceral, and skeletal involvement, and biomarkers. Specific radiologic imaging techniques are recommended for evaluating visceral and skeletal pathology. All patients should undergo comprehensive regular assessment, the frequency of which depends on treatment status and whether therapeutic goals have been achieved. Additionally, reassessment should be performed whenever enzyme therapy dose is altered, or in case of significant clinical complication.
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- Yildiz, Yildiz, et al.
(författare)
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Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease
- 2013
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gaucher disease (GD) is the most common inherited lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1). GD is clinically heterogeneous and although the type of GBA1 mutation plays a role in determining the type of GD, it does not explain the clinical variability seen among patients. Cumulative evidence from recent studies suggests that GBA2 could play a role in the pathogenesis of GD and potentially interacts with GBA1. Methods: We used a framework of functional and genetic approaches in order to further characterize a potential role of GBA2 in GD. Glucosylceramide (GlcCer) levels in spleen, liver and brain of GBA2-deficient mice and mRNA and protein expression of GBA2 in GBA1-deficient murine fibroblasts were analyzed. Furthermore we crossed GBA2-deficient mice with conditional Gba1 knockout mice in order to quantify the interaction between GBA1 and GBA2. Finally, a genetic approach was used to test whether genetic variation in GBA2 is associated with GD and/or acts as a modifier in Gaucher patients. We tested 22 SNPs in the GBA2 and GBA1 genes in 98 type 1 and 60 type 2/3 Gaucher patients for single-and multi-marker association with GD. Results: We found a significant accumulation of GlcCer compared to wild-type controls in all three organs studied. In addition, a significant increase of Gba2-protein and Gba2-mRNA levels in GBA1-deficient murine fibroblasts was observed. GlcCer levels in the spleen from Gba1/Gba2 knockout mice were much higher than the sum of the single knockouts, indicating a cross-talk between the two glucosylceramidases and suggesting a partially compensation of the loss of one enzyme by the other. In the genetic approach, no significant association with severity of GD was found for SNPs at the GBA2 locus. However, in the multi-marker analyses a significant result was detected for p.L444P (GBA1) and rs4878628 (GBA2), using a model that does not take marginal effects into account. Conclusions: All together our observations make GBA2 a likely candidate to be involved in GD etiology. Furthermore, they point to GBA2 as a plausible modifier for GBA1 in patients with GD.
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