Screening for the Transthyretin-Related Familial Amyloidotic Small Fiber Polyneuropathy (TRAP2)
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||TTR-FAP Screening - Screening for the Transthyretin-Related Familial Amyloidotic Small Fiber Polyneuropathy - a International, Multicentre, Epidemiological Protocol|
|Study Start Date:||November 2016|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||December 2019 (Final data collection date for primary outcome measure)|
all adult patients at 18 years with small fiber 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
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 mutations are known to cause the disease, the most common amino acid change is V30M.
The mutation in the TTR gene causes the destabilization of the physiologically tetrameric protein. Usually transthyretin consists of four identical monomeric subunits and binds the thyroxin circulating in the blood plasma. The monomeric subunits exhibit a pronounced β-sheet structure which leads to the accumulation of unsoluble β-fibrils when they are destabilised as in TTR-FAP.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01705626
|Contact: Arndt Rolfs, MD||49-381-494 ext email@example.com|
|Contact: Susanne Zielke||49-381-494 ext firstname.lastname@example.org|
|Principal Investigator:||Arndt Rolfs, MD||University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration|