High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly

Sekijima, Yoshiki; Uchiyama, Shigeharu; Tojo, Koji; Sakai, Kenji; Shimizu, Yoshifusa; Imaeda, Toshihiko; Hoshii, Yoshibonu; Kato, Hiroyuki; Ikeda, Shu‐ichi

doi:10.1016/j.humpath.2011.03.004

Cited by 137 publications

(102 citation statements)

References 20 publications

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“…Renal involvement is not rare although underdiagnosed and may be of clinical relevance (38). Carpal tunnel syndrome is commonly associated with connective tissue deposition of amyloid and has been suggested sometimes to be a first sign of SSA (39). Carpal tunnel syndrome has been reported to occur up to decades before other symptoms of disease in mutant ATTR amyloidosis, such as the Danish TTR L111M mutation (40).…”

Section: Discussionmentioning

confidence: 99%

Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis

Westermark

Suhr

et al. 2014

Upsala Journal of Medical Sciences

130

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Background Senile systemic amyloidosis (SSA) derived from wild-type transthyretin is a fairly common condition of old individuals, particularly men. The main presentation is by cardiac involvement, which can lead to severe restrictive cardiomyopathy. SSA is, however, a systemic disease, and amyloid deposits may appear in many other tissues but are thought to be without clinical symptoms outside the heart. Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs.Results We questioned whether lumbar spinal stenosis sometimes could be a manifestation of undiagnosed SSA. In this first report we have studied the presence of amyloid in material obtained at surgery for spinal stenosis in 26 patients. Amyloid was found in 25 subjects. Transthyretin was demonstrated immunohistochemically in 5 out of 15 studied resected tissues. Four of the positive materials were analyzed with Western blot revealing both full-length transthyretin (TTR) and C-terminal TTR fragments, typically seen in SSA.Conclusion We conclude that lumbar spinal stenosis quite frequently may be a consequence of SSA and that further studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis

Westermark

Suhr

et al. 2014

Upsala Journal of Medical Sciences

130

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“…An important pointer to the diagnosis is carpal tunnel syndrome, which is the only reported extra-cardiac manifestation of SSA. Up to 34% of tissue samples obtained during decompression of carpal tunnel syndrome in the older population demonstrate wild-type TTR deposition, encouraging histological study in all cases 18. A history of carpal tunnel syndrome often predates SSA by some years, and should be considered a red flag in older patients presenting with heart failure and left ventricular wall thickening 19…”

Section: Subtypesmentioning

confidence: 95%

Cardiac transthyretin amyloidosis

Dungu

Anderson

Whelan

et al. 2012

Heart

114

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Cardiac amyloidosis of transthyretin fibril protein (ATTR) type is an infiltrative cardiomyopathy characterised by ventricular wall thickening and diastolic heart failure. Increased access to cardiovascular magnetic resonance imaging has led to a marked increase in referrals to our centre of Caucasian patients with wild-type ATTR (senile systemic) amyloidosis and Afro-Caribbean patients with the hereditary ATTR V122I type. Both subtypes present predominantly as isolated cardiomyopathy. The differential diagnosis includes cardiac amyloid light-chain (AL) amyloidosis, which has a poorer prognosis and can be amenable to chemotherapy. We review here the clinical features of cardiac ATTR amyloidosis and describe the diagnostic tests to determine ATTR type. Correct diagnosis is ever more crucial given that several novel therapies for ATTR amyloidosis are on the near horizon.

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“…Postmortem studies demonstrated that the prevalence of SSA was 12–25% in patients older than 80 years [19,20]. Furthermore, recent studies determined that WT TTR amyloid may also cause several other disorders and conditions [12], such as radiculomyelopathy [36], tongue necrosis [37], hematuria [38], nodular amyloid deposits in the lung [39], and frequent amyloid deposition in ligaments and tendons such as carpal tunnel and spinal ligaments [40,41], to a degree not previously known. In addition to full-length WT TTR, truncated C-terminal WT TTR fragments starting at positions 46–52 are usually detected in amyloid deposits obtained from SSA patients [32,35].…”

Section: Introductionmentioning

confidence: 99%

Recent advances in transthyretin amyloidosis therapy

Ueda

Ando

2014

Transl Neurodegener

119

113

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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.

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High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly

Cited by 137 publications

References 20 publications

Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis

Transthyretin-derived amyloidosis: Probably a common cause of lumbar spinal stenosis

Cardiac transthyretin amyloidosis

Recent advances in transthyretin amyloidosis therapy

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