Medicine:Familial amyloid neuropathy
| Familial amyloid neuropathy |
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The familial amyloid neuropathies (or familial amyloidotic neuropathies, neuropathic heredofamilial amyloidosis, familial amyloid polyneuropathy) are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other nerves are compromised by protein aggregation and/or amyloid fibril formation.[1][2][3]
Classification
The aggregation of one precursor protein leads to peripheral neuropathy and/or autonomic nervous system dysfunction. These proteins include: transthyretin (ATTR, the most commonly implicated protein), apolipoprotein A1, and gelsolin.[4]
Due to the rareness of the other types of familial neuropathies, transthyretin amyloidogenesis-associated polyneuropathy should probably be considered first.[5]
"FAP-I" and "FAP-II" are associated with transthyretin.[1][6] (Senile systemic amyloidosis [abbreviated "SSA"] is also associated with transthyretin aggregation.)
"FAP-III" is also known as "Iowa-type", and involves apolipoprotein A1.[7]
"FAP-IV" is also known as "Finnish-type", and involves gelsolin.[8]
Fibrinogen, apolipoprotein A1, and lysozyme are associated with a closely related condition, familial visceral amyloidosis.
Diagnosis is confirmed by blood tests, organ biopsies, and tissue biopsies. Genetic testing can also be used to confirm a mutation in the TTR gene. Although some people with a hATTR gene mutation may not experience symptoms.
Treatment
Liver transplantation has proven to be effective for ATTR familial amyloidosis due to Val30Met mutation.[9]
In 2011 the European Medicines Agency approved tafamidis for this condition.[10] The FDA rejected the application for marketing approval in the US in 2012 on the basis that the clinical trial data did not show efficacy based on a functional endpoint, and the FDA requested further clinical trials.[11]
References
- ↑ 1.0 1.1 Andrade C (September 1952). "A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves". Brain 75 (3): 408–27. doi:10.1093/brain/75.3.408. PMID 12978172.
- ↑ Kelly JW (February 1996). "Alternative conformations of amyloidogenic proteins govern their behavior". Curr. Opin. Struct. Biol. 6 (1): 11–7. doi:10.1016/S0959-440X(96)80089-3. PMID 8696966.
- ↑ Dobson CM (December 2003). "Protein folding and misfolding". Nature 426 (6968): 884–90. doi:10.1038/nature02261. PMID 14685248. Bibcode: 2003Natur.426..884D.
- ↑ "The expanding superfamily of gelsolin homology domain proteins". Cytoskeleton 70 (11): 775–95. 2013. doi:10.1002/cm.21149. PMID 24155256.
- ↑ "Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy". Medicine (Baltimore) 85 (4): 229–38. July 2006. doi:10.1097/01.md.0000232559.22098.c3. PMID 16862048.
- ↑ "Amyloid". http://neuromuscular.wustl.edu/nother/amyloid.htm#transthyretin.
- ↑ "Amyloid". http://neuromuscular.wustl.edu/nother/amyloid.htm#apo1.
- ↑ "Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy type IV". Ophthalmology 103 (7): 1106–10. July 1996. doi:10.1016/s0161-6420(96)30560-5. PMID 8684801.
- ↑ "ATTR Famililial Amyloidosis". BU – Amyloid Treatment & Research Program. http://www.bu.edu/amyloid/doctors/features/clinical-attr.html.
- ↑ Said, G; Grippon, S; Kirkpatrick, P (1 March 2012). "Tafamidis.". Nature Reviews. Drug Discovery 11 (3): 185–6. doi:10.1038/nrd3675. PMID 22378262.
- ↑ Grogan, Kevin (19 June 2012). "FDA rejects Pfizer rare disease drug tafamidis" (in en). Pharma Times. http://www.pharmatimes.com/news/fda_rejects_pfizer_rare_disease_drug_tafamidis_977149.
External links
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