Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation

Oshima, Toshinori; Kawahara, Satomi; Ueda, Mitsuharu; Kawakami, Yasuto; Tanaka, Rina; Okazaki, Taro; Misumi, Yohei; Obayashi, Konen; Yamashita, Taro; Ohya, Yuki; Ihse, Elisabet; Shinriki, Satoru; Tasaki, Masayoshi; Jono, Hirofumi; Asonuma, Katsuhiro; Inomata, Yukihiro; Westermark, Per; Ando, Yumiko

doi:10.1136/jnnp-2013-305973

Cited by 47 publications

(42 citation statements)

References 35 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is, therefore, tempting to speculate that mut-TTR, secreted by the choroid plexus, may deposit extensively in the CNS of these patients given the necessary time frame. In fact, Oshima et al 40 have recently found that, in the CNS TTR amyloid deposits (spinal cord) from five LT ATTR-V30M patients, mut-TTR outweighed Wt-TTR (86% vs 14%), in contrast to the peripheral deposits where Wt-TTR predominated. The same was observed in TTR brain deposits of patients from a family with meningeal-vascular amyloidosis (ATTR-G53R) including patients presenting FNEs 31…”

Section: Discussionmentioning

confidence: 97%

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

Maia

Magalhães

Freitas

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

106

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

Maia

Magalhães

Freitas

et al. 2014

Journal of Neurology, Neurosurgery & Psychiatry

106

View full text Add to dashboard Cite

show abstract

“…The main causes of death in patients after orthotopic LTs involved cardiac problems (24%), sepsis (23%), and liver-related complications (14%) [66,70,71]. Although clinical evaluations indicated that progression of other clinical symptoms such as peripheral neuropathy [73,74], GI symptoms [75], and renal involvement [72,76] usually stopped after LT in FAP ATTR Val30Met patients, other studies suggested that LT failed to prevent progression of cardiac amyloidosis in FAP ATTR Val30Met patients after LT [69,77], with this failure reportedly being due to continued formation of amyloid mainly derived from WT TTR secreted from the transplanted normal liver graft [29,30,78]. However, why WT TTR amyloid deposits, which are usually found in elderly people with SSA, occur in some tissue sites of FAP patients after LT remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in transthyretin amyloidosis therapy

Ueda

Ando

2014

Transl Neurodegener

120

113

View full text Add to dashboard Cite

Mutant (MT) forms of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis—familial amyloidotic polyneuropathy (FAP). Until 20 years ago, FAP was thought to be an endemic disease, but FAP is known to occur worldwide. To date, more than 130 mutations in the TTR gene have been reported. Genotype-phenotype correlations are seen in FAP, and some variation in clinical presentation is often observed in individual kindreds with the same mutation and even among family members. Of the pathogenic TTR mutations, Val30Met was the first to be identified and is the most frequent known mutation found throughout the world. Studies of patients with FAP amyloidogenic TTR (ATTR) Val30Met documented sensorimotor polyneuropathy, autonomic dysfunction, heart and kidney failure, gastrointestinal tract (GI) disorders, and other symptoms leading to death, usually within 10 years of the onset of disease. Diagnosis is sometimes delayed, especially in patients without a clear family history and typical clinical manifestations, since diagnosis requires various studies and techniques such as histopathology, genetic testing, and mass spectrometry. For treatment of FAP, liver transplantation (LT) reportedly halts the progression of clinical manifestations. Exchange of an FAP patient’s diseased liver with a healthy liver causes MT TTR in the body to be replaced by wild-type (WT) TTR. Although clinical evaluations indicated that progression of other clinical symptoms such as peripheral neuropathy, GI symptoms, and renal involvement usually halted after LT in FAP ATTR Val30Met patients, recent studies suggested that LT failed to prevent progression of cardiac amyloidosis in FAP ATTR Val30Met patients after LT, with this failure reportedly being due to continued formation of amyloid that derived mainly from WT TTR secreted from the transplanted non-mutant liver graft. In recent years, many therapeutic strategies have been proposed, and several ongoing therapeutic trials involve, for example, stabilizers of TTR tetramers (tafamidis and diflunisal) and gene therapies to suppress TTR expression (antisense methods and use of small interfering RNAs). These novel therapies may prove to prevent progression of FAP.

show abstract

“…The paper by Oshima et al 5 investigated amyloid deposition in patients with FAP ATTR Val30Met with a focus on the long-term effects of liver transplantation (LT). The amount of amyloid deposition, the proportion of wild-type TTR in amyloid deposits, and the presence of TTR truncations in amyloid deposits were determined in various organs of four autopsied cases that had survived for more than a decade after LT, with three of them being early onset cases from endemic foci.…”

mentioning

confidence: 99%

What is the prototype of familial amyloid polyneuropathy?

Koike

Sobue

2013

Journal of Neurology, Neurosurgery & Psychiatry

View full text Add to dashboard Cite

Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation

Abstract: FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.

Cited by 47 publications

References 35 publications

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings

Recent advances in transthyretin amyloidosis therapy

What is the prototype of familial amyloid polyneuropathy?

Contact Info

Product

Resources

About