Orphanet J Rare Dis
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Orphanet J Rare Dis · Apr 2013
Clinical and molecular characterization of 40 patients with classic Ehlers-Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.
Classic Ehlers-Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. ⋯ Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS.
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Orphanet J Rare Dis · Feb 2013
Impact of Friedreich's Ataxia on health-care resource utilization in the United Kingdom and Germany.
Friedreich's Ataxia (FRDA) is a neurodegenerative disorder that causes progressive damage to the central and peripheral nervous systems having a significant impact upon quality of life. With little information in the literature, cross-sectional observational studies were conducted in the UK and Germany to collect data on resource use and the burden of the disease on individuals and their caregivers. ⋯ It is hoped that these estimates of resource utilization, can help in understanding the previously unquantified burden of FRDA. Given the long disease duration, management strategies should seek to minimise the impact of the condition on individuals and their caregivers, while maximising quality of life.
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Orphanet J Rare Dis · Jan 2013
ReviewGuideline of transthyretin-related hereditary amyloidosis for clinicians.
Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. ⋯ This article aims to help physicians better understand transthyretin amyloidosis--and, specifically, familial amyloidotic polyneuropathy--so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials.
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Orphanet J Rare Dis · Jan 2013
Behçet's disease: new insight into the relationship between procoagulant state, endothelial activation/damage and disease activity.
Behçet disease (BD) is associated with a prothrombotic state of unknown origin that may lead to life-threatening events. Calibrated Automated Thrombogram (CAT) and Rotational Thromboelastometry (ROTEM) are two global haemostasis assays that may reveal new insights into the physiopathological mechanisms of the disease and its procoagulant condition. ⋯ Both ROTEM and CAT tests reveal that patients with BD have a procoagulant state even in the absence of thrombosis. ROTEM test indicates that increased levels of fibrinogen and PAI-1 may be involved in the prothrombotic state of this pathology, while platelets do not significantly contribute. Moreover, CAT assay demonstrate that plasma from BD patients is able to generate more thrombin than controls in response to the same stimulus and that this effect is independent of the DA and the endothelial impairment suggesting the involvement of another factor in the hypercoagulable state observed in BD patients. This study also shows that endothelium activation/damage may be a contributing factor in both the procoagulant and clinical conditions of BD, as shown by the direct correlation between ES levels, ROTEM parameters and DA.
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Orphanet J Rare Dis · Jan 2013
Randomized Controlled Trial Multicenter StudyUrsodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial.
Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. ⋯ Celecoxib reduces duodenal polyp density in patients with FAP, and unexpectedly, high dose UDCA co-treatment counteracts this effect. The benefit of long term use of celecoxib for duodenal cancer prevention needs to be weighed against the (risk of) adverse events.