289:, FAP is invariably fatal, usually within a decade. The disadvantage of liver transplantation is that approximately 10% of the subjects die from the procedure or complications resulting from the procedure, which is a form of gene therapy wherein the liver expressing wild-type and mutant TTR is replaced by a liver only expressing wild-type TTR. Moreover, transplanted patients must take immune suppressants (medications) for the remainder of their life, which can lead to additional complications.
256:'s Peripheral and Central Nervous System Drugs Advisory Committee rejected the drug in June 2012, in a 13–4 vote. The committee stated that there was not enough evidence supporting efficacy of the drug, and requested additional clinical trials. In May 2019, the FDA approved two tafamidis preparations for the treatment of transthyretin-mediated cardiomyopathy, but has not approved it for the treatment of transthyretin familial amyloid polyneuropathy.
48:
191:. A replacement of valine by methionine at position 30 (TTR V30M) is the mutation most commonly found in FAP. The transthyretin protein is a tetramer. The tetramer has to dissociate into misfolded monomers to aggregate into a variety of structures including amyloid fibrils. Because most patients are heterozygotes, they deposit both mutant and wild type TTR subnits.
230:. Occasionally, biopsy of skin, nerve, or muscle may be performed, which can show signs of denervation and amyloid deposition with response to anti-TTR antibodies. Additional testing should be performed to identify involvement of the heart or kidneys.
659:
Lefaucheur, J. P.; Zouari, H. G.; Gorram, F.; Nordine, T.; Damy, T.; & Planté-Bordeneuve, V. (2018). "The value of electrochemical skin conductance measurement using
Sudoscan® in the assessment of patients with familial amyloid polyneuropathy".
304:
in 2010) for the treatment of FAP based on clinical trial data. Tafamidis (20 mg once daily) slowed the progression of FAP over a 36-month period and importantly reversed the weight loss and muscle wasting associated with disease progression.
329:), with more than 1000 affected people, coming from about 500 families, where 70% of the people develop the illness. All the analysed Portuguese families presented the same haplotype (haplotype I) associated with the Met 30 mutation. In northern
809:
689:
Castro, J.; Costa, J.; de Castro, I.; & Conceição, I. (2018). "Electrochemical skin conductance in hereditary amyloidosis related to transthyretin V30M–a promising tool to assess treatment efficacy?".
992:
Dardiotis, Eftymioe; Koutsou, Panoelitsa; Papanicolaou, Eleni Zamba; Vonta, Ilia; Kladi, Athina; Vassilopoulos, Demetrios; Hadjigeorgiou, Georgios; Christodoulou, Kyproyla; Kyriakides, Theodoros (2009).
1435:
503:
Adams, David; Ando, Yukio; Beirão, João Melo; Coelho, Teresa; Gertz, Morie A.; Gillmore, Julian D.; Hawkins, Philip N.; Lousada, Isabelle; Suhr, Ole B.; Merlini, Giampaolo (6 January 2020).
816:
218:
typically shows an axonal polyneuropathy, with sensory involvement greater than motor. Superimposed mononeuropathies may also be evident, such as a median mononeuropathy at the wrist (
346:
The disease is somewhat prevalent in Cyprus. Mean age of onset was 46 years, and penetrance is estimated to be 28%, both of which differ from the
Portuguese and Swedish populations.
343:, the Skellefteå disease), 1.5% of the population has the mutated gene. There are many other populations in the world who exhibit the illness after having developed it independently.
864:
252:
has been approved for the treatment of transthyretin familial amyloid polyneuropathy in Europe. Studies have found that it delays neurological problems when started early. The US
419:
Andrade C (September 1952). "A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves".
834:
198:(chromosome 18 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.
1251:
226:(EMG) may show evidence of chronic denervation and reinnervation. Autonomic testing, including quantitative sweat testing, can reveal involvement of the
888:
274:
system. Researchers reported mild adverse events and decreases in serum misfolded transthyretin protein concentrations through targeted knockout.
1430:
1129:
1236:
1059:
484:
365:
963:
194:
FAP is inherited in an autosomal dominant manner. This means that the defective gene responsible for the disorder is located on an
237:
1425:
110:
454:
Coles LS, Young RD (May 2012). "Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension".
270:
In August 2021 six patients with hereditary ATTR amyloidosis with polyneuropathy were given doses of NTLA-2001, based on a
1338:
815:. U.S. Food and Drug Administration Center for Drug Evaluation and Research Division of Neurology Products. Archived from
1246:
969:
842:
253:
206:
Clinical suspicion for FAP is raised on the basis of a family history of neuropathy and physical exam showing signs of
1297:
1292:
1276:
384:
Ando Y, Ueda M (May 2008). "Novel methods for detecting amyloidogenic proteins in transthyretin related amyloidosis".
865:"FDA approves new treatments for heart disease caused by a serious rare disease, transthyretin mediated amyloidosis"
1320:
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17:
1302:
314:
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215:
286:
188:
142:
1420:
1166:
1115:
556:"Quantitative sensation and autonomic test abnormalities in transthyretin amyloidosis polyneuropathy"
113:(SSA), which is not inherited, and which was determined to be the primary cause of death for 70% of
1171:
271:
1022:
945:
791:
748:
707:
677:
92:
318:
505:"Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy"
1014:
995:"Epidemiological, clinical and genetic study of familial amyloidotic polyneuropathy in Cyprus"
937:
783:
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703:
673:
642:
624:
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536:
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436:
401:
138:
95:
60:
766:
Scott LJ (August 2014). "Tafamidis: a review of its use in familial amyloid polyneuropathy".
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114:
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to identify mutations in the TTR gene, but may include other corroborative investigation.
211:
1088:
554:
Kim, Dong Hwee; Zeldenrust, Steven R.; Low, Phillip A.; Dyck, Peter J. (September 2009).
277:
Eplontersen (Wainua) was approved for medical use in the United States in
December 2023.
47:
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1226:
637:
604:
580:
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504:
169:
106:
1414:
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1026:
949:
723:
Adams, D; Cauquil, C; Labeyrie, C (October 2017). "Familial amyloid polyneuropathy".
334:
322:
181:
158:
154:
80:
795:
1378:
1176:
752:
296:
approved the transthyretin kinetic stabilizer
Tafamidis or Vyndaqel discovered by
129:
Usually manifesting itself between 20 and 40 years of age, it is characterized by
736:
55:
Familial amyloid polyneuropathy has an autosomal dominant pattern of inheritance.
1284:
1270:
1138:
463:
134:
103:
99:
83:
521:
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330:
301:
1103:
GeneReviews/NIH/NCBI/UW entry on
Familial Transthyretin Amyloidosis
267:-based treatment, at an expected cost of up to $ 450,000 per year.
1210:
264:
150:
397:
153:
are affected. FAP is characterized by the systemic deposition of
1064:
916:"CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis"
488:
369:
130:
1111:
1107:
889:"Rare-Disease Treatment From Alnylam to Cost $ 450,000 a Year"
240:
may provide a measure of subclinical autonomic involvement.
835:"FDA Delivers CRL for Pfizer's Rare Disease Drug Vyndaqel"
603:
Shin, Susan C.; Robinson-Papp, Jessica (November 2012).
915:
370:
Amyloidosis, hereditary, transthyretin-related - 105210
102:, and was first identified and described by Portuguese
300:
and developed by FoldRx pharmaceuticals (acquired by
1041:
1436:
Skin conditions resulting from errors in metabolism
1352:
1329:
1311:
1283:
1269:
1260:
1219:
1145:
1074:
1045:
121:. FAP can be ameliorated by liver transplantation.
59:
37:
32:
87:abbreviated also as ATTR (hereditary form), or
1123:
609:The Mount Sinai Journal of Medicine, New York
338:
8:
76:transthyretin-related hereditary amyloidosis
18:Transthyretin-related hereditary amyloidosis
810:"Vyndaqel (tafamidis meglumine) NDA 202737"
1266:
1130:
1116:
1108:
1042:
863:Commissioner, Office of the (2020-03-24).
168:, causing a progressive sensory and motor
46:
29:
931:
718:
716:
636:
579:
530:
520:
379:
377:
355:
914:Gillmore, Julian D. (August 5, 2021).
361:
359:
1298:ACys+ABri/Cerebral amyloid angiopathy
1252:ATTR/Transthyretin-related hereditary
841:. Clarivate Analytics. Archived from
7:
920:The New England Journal of Medicine
485:Online Mendelian Inheritance in Man
366:Online Mendelian Inheritance in Man
180:FAP is caused by a mutation of the
25:
964:"Eplontersen: FDA-Approved Drugs"
259:In August 2018, the FDA approved
702::10.1080/13506129.2018.1545639.
238:electrochemical skin conductance
109:, in 1952. FAP is distinct from
1321:AApoA1+AFib+ALys/Familial renal
1247:AA/Familial Mediterranean fever
672::10.1016/j.clinph.2018.05.005.
72:Familial amyloid polyneuropathy
33:Familial amyloid polyneuropathy
210:. Diagnosis can be made using
1:
1367:ACal/Medullary thyroid cancer
1339:Primary cutaneous amyloidosis
1237:Aβ2M/Haemodialysis-associated
145:. In its terminal state, the
107:Mário Corino da Costa Andrade
1431:Autosomal dominant disorders
970:Food and Drug Administration
737:10.1097/WCO.0000000000000476
725:Current Opinion in Neurology
489:Transthyretin (TTR) - 176300
254:Food and Drug Administration
1293:Familial amyloid neuropathy
464:10.1016/j.ypmed.2012.03.003
458:. 54 Suppl (Suppl): S9–11.
111:senile systemic amyloidosis
89:Corino de Andrade's disease
1452:
522:10.1007/s00415-019-09688-0
1262:Organ-limited amyloidosis
1011:10.1080/13506120802676948
780:10.1007/s40265-014-0260-2
294:European Medicines Agency
166:peripheral nervous system
98:disease. It is a form of
54:
45:
662:Clinical Neurophysiology
317:in Portuguese locations
228:autonomic nervous system
216:Nerve conduction testing
386:Frontiers in Bioscience
184:gene, located on human
1426:Neurological disorders
1303:Aβ/Alzheimer's disease
605:"Amyloid Neuropathies"
433:10.1093/brain/75.3.408
339:
337:(it is locally called
220:carpal tunnel syndrome
933:10.1056/NEJMoa2107454
143:autonomic dysfunction
1277:AANF/Isolated atrial
1220:Systemic amyloidosis
509:Journal of Neurology
333:, more specifically
285:In the absence of a
164:, especially in the
456:Preventive Medicine
272:CRISPR gene editing
1075:External resources
560:Muscle & Nerve
292:In late 2011, the
93:autosomal dominant
1408:
1407:
1404:
1403:
1379:APro/Prolactinoma
1242:AGel/Finnish type
1098:
1097:
822:on 28 April 2017.
621:10.1002/msj.21352
572:10.1002/mus.21332
236:function through
139:muscular weakness
115:supercentenarians
96:neurodegenerative
69:
68:
27:Medical condition
16:(Redirected from
1443:
1391:AIAPP/Insulinoma
1267:
1150:forming proteins
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1125:
1118:
1109:
1043:
1031:
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989:
983:
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895:. 10 August 2018
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668:(8): 1565–1569.
657:
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593:
583:
551:
545:
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534:
524:
515:(6): 2109–2122.
500:
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410:
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381:
372:
363:
342:
313:This disease is
298:Jeffery W. Kelly
287:liver transplant
224:Electromyography
157:variants of the
50:
30:
21:
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1450:
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1396:Type 2 diabetes
1348:
1344:Amyloid purpura
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392:(13): 5548–58.
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340:Skelleftesjukan
319:Póvoa de Varzim
311:
283:
248:The medication
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212:genetic testing
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127:
28:
23:
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15:
12:
11:
5:
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1264:
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1239:
1234:
1232:AA amyloidosis
1229:
1227:AL amyloidosis
1223:
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1089:article/335301
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1046:Classification
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1038:External links
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1033:
1032:
984:
955:
926:(6): 493–502.
906:
880:
855:
833:Pihl-Carey K.
825:
801:
774:(12): 1371–8.
758:
731:(5): 481–489.
712:
698:(4): 267–268.
682:
652:
615:(6): 733–748.
595:
566:(3): 363–370.
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170:polyneuropathy
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117:who have been
74:, also called
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845:on 2017-12-01
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427:(3): 408–27.
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323:Vila do Conde
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155:amyloidogenic
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81:transthyretin
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19:
1082:
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1005:(1): 32–37.
1002:
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987:
975:. Retrieved
967:
958:
923:
919:
909:
897:. Retrieved
892:
883:
872:. Retrieved
868:
858:
847:. Retrieved
843:the original
838:
828:
817:the original
804:
771:
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728:
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398:10.2741/3098
389:
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312:
309:Epidemiology
291:
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247:
232:
205:
193:
189:18q12.1-11.2
179:
128:
125:Presentation
88:
79:
75:
71:
70:
1421:Amyloidosis
1139:Amyloidosis
977:21 December
135:paresthesia
104:neurologist
100:amyloidosis
84:amyloidosis
38:Other names
1415:Categories
874:2023-01-25
849:2012-12-03
706:30773060.
676:29883834.
350:References
335:Skellefteå
244:Treatments
208:neuropathy
186:chromosome
1374:Pituitary
1354:Endocrine
1084:eMedicine
1027:205766147
950:235722446
899:11 August
710:73476147.
629:0027-2507
281:Prognosis
261:patisiran
250:tafamidis
234:Sudomotor
202:Diagnosis
119:autopsied
65:Neurology
61:Specialty
1386:Pancreas
1019:19291512
942:34215024
839:BioWorld
796:24612955
788:25022953
745:28678039
680:47011006
647:23239211
590:19618439
541:31907599
487:(OMIM):
472:22579241
441:12978172
406:18508604
368:(OMIM):
196:autosome
149:and the
91:, is an
1362:Thyroid
1148:amyloid
1146:Common
999:Amyloid
753:4968350
692:Amyloid
638:3531896
581:2735590
532:8179912
327:Caxinas
315:endemic
162:protein
147:kidneys
1313:Kidney
1065:105210
1025:
1017:
948:
940:
794:
786:
751:
743:
645:
635:
627:
588:
578:
539:
529:
470:
439:
404:
331:Sweden
302:Pfizer
1285:Brain
1271:Heart
1186:AIAPP
1023:S2CID
972:(FDA)
968:U.S.
946:S2CID
820:(PDF)
813:(PDF)
792:S2CID
768:Drugs
749:S2CID
708:S2CID
678:S2CID
421:Brain
265:siRNA
263:, an
176:Cause
151:heart
1331:Skin
1211:ABri
1206:ACys
1201:AANF
1196:APro
1191:ACal
1167:Aβ2M
1162:ATTR
1060:OMIM
1015:PMID
979:2023
938:PMID
901:2018
784:PMID
741:PMID
704:PMID
674:PMID
643:PMID
625:ISSN
586:PMID
537:PMID
468:PMID
437:PMID
402:PMID
321:and
141:and
131:pain
1181:APP
1007:doi
928:doi
924:385
869:FDA
776:doi
733:doi
700:doi
670:doi
666:129
633:PMC
617:doi
576:PMC
568:doi
527:PMC
517:doi
513:268
460:doi
429:doi
394:doi
222:).
182:TTR
41:FAP
1417::
1177:Aβ
1172:AL
1157:AA
1087::
1063::
1021:.
1013:.
1003:16
1001:.
997:.
966:.
944:.
936:.
922:.
918:.
891:.
867:.
837:.
790:.
782:.
772:74
770:.
747:.
739:.
729:30
727:.
715:^
696:25
694:.
664:.
641:.
631:.
623:.
613:79
611:.
607:.
584:.
574:.
564:40
562:.
558:.
535:.
525:.
511:.
507:.
495:^
466:.
435:.
425:75
423:.
400:.
390:13
388:.
376:^
358:^
172:.
137:,
133:,
78:,
1179:/
1131:e
1124:t
1117:v
1052:D
1029:.
1009::
981:.
952:.
930::
903:.
877:.
852:.
798:.
778::
755:.
735::
649:.
619::
592:.
570::
543:.
519::
474:.
462::
443:.
431::
408:.
396::
325:(
20:)
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