Familial amyloid neuropathy

Familial amyloid neuropathy
SpecialtyEndocrinology Edit this on Wikidata

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. ^ a b 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.
  2. ^ 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.
  3. ^ Dobson CM (December 2003). "Protein folding and misfolding". Nature. 426 (6968): 884–90. Bibcode:2003Natur.426..884D. doi:10.1038/nature02261. PMID 14685248. S2CID 1036192.
  4. ^ Ghoshdastider U, Popp D, Burtnick LD, Robinson RC (2013). "The expanding superfamily of gelsolin homology domain proteins". Cytoskeleton. 70 (11): 775–95. doi:10.1002/cm.21149. PMID 24155256. S2CID 205643538.
  5. ^ Delahaye N, Rouzet F, Sarda L, et al. (July 2006). "Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy". Medicine (Baltimore). 85 (4): 229–38. doi:10.1097/01.md.0000232559.22098.c3. PMID 16862048. S2CID 25723585.
  6. ^ "Amyloid".
  7. ^ "Amyloid".
  8. ^ Akiya S, Nishio Y, Ibi K, et al. (July 1996). "Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy type IV". Ophthalmology. 103 (7): 1106–10. doi:10.1016/s0161-6420(96)30560-5. PMID 8684801.
  9. ^ "ATTR Famililial Amyloidosis". BU – Amyloid Treatment & Research Program. Archived from the original on 2008-07-06.
  10. ^ Said, G; Grippon, S; Kirkpatrick, P (1 March 2012). "Tafamidis". Nature Reviews. Drug Discovery. 11 (3): 185–6. doi:10.1038/nrd3675. PMID 22378262. S2CID 256746210.
  11. ^ Grogan, Kevin (19 June 2012). "FDA rejects Pfizer rare disease drug tafamidis". Pharma Times.