Clinical Trial: Screening for the Transthyretin-Related Familial Amyloidotic Small Fiber Polyneuropathy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: TTR-FAP Screening - Screening for the Transthyretin-Related Familial Amyloidotic Small Fiber Polyneuropathy - a International, Multicentre, Epidemiological Protocol

Brief Summary: The purpose of this study is to determine the prevalence of patients with a polyneuropathy of undetermined etiology based on the normal results of laboratory data (CRP, glucose, electrolytes, urea,transaminases, TSH, immunoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia) no anamnesis for carcinoma, no continuous alcohol consumption; no light-chain-amyloidosis; no anamnesis for heavy metal exposure.

Detailed Summary:

Neuropathies are generalised disorders of the peripheral nervous system, due to deranged function of the peripheral motor, sensory and autonomic neurons, their fibres or their myelin sheath. Dysfunction of unmyelinated C and myelinated Aδ fibres causes symptoms like insensitivity or hypersensitivity to heat and/or cold and neuropathic pain. These fibres have slow conduction velocities, carrying temperature feeling and pain sensations from nociceptors and thermoreceptors respectively. An isolated disturbance of these fibres leads usually to the diagnosis of small fibre neuropathy (SFN). The pathogenesis of SFN may be of inflammatory, autoimmune, metabolic, toxic or hereditary nature. Careful clinical and electrodiagnostic assessment, with attention to the pattern of involvement and the types of nerve fibers most affected, narrows the differential diagnosis and helps to focus the laboratory evaluation.

Beside the frequent genetic etiologies in PNP (pmp22, MFN2) one cause of a genetic polyneuropathy may be a hereditary amyloidosis. These have been described as endemic in Sweden, Portugal or Japan. The most common form of the hereditary familial amyloidotic neuropathy (FAP) is the Transthyretin-related FAP, however two other amyloidogenic proteins have been described: Apolipoprotein A-I and Gelsolin (Ando et al., 2005; Adams et al., 2010). This study focuses on TTR-FAP (OMIM: #105210, OMIM: *176300), whose prevalence shall be determined in a cohort of 500 patients with polyneuropathy of unknown etiology. The TTR-FAP is an autosomal dominant disease, the exact prevalence of which is unknown but estimated to be around 1:100,000 to 1:1,000,000 in the normal population (Orphanet, ORPHA 85447). While the diagnosis of the amyloidotic neuropathy can be conducted histologically, a molecular genetic approach is necessary to diagnose TTR-FAP. Even though more than 100 point mutati
Sponsor: University of Rostock

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Information By: University of Rostock

Dates:
Date Received: October 9, 2012
Date Started: December 2016
Date Completion: December 2019
Last Updated: May 10, 2017
Last Verified: May 2017