Sequential (domino) transplantation of the liver in a transthyretin-50 familial amyloid polyneuropathy

Golling, M.; Singer, Reinhard; Weiss, G.; Mehrabi, Arianeb; Zapletal, C.; Kraus, Thomas; Herfarth, Christian; Klar, E.

doi:10.1007/s004230050005

Cited by 16 publications

(8 citation statements)

References 17 publications

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“…This technique has been named ''domino liver transplantation (DLT)'' and can be considered in patients with selected genetic or biochemical disorders. The liver must be fully functional and the genetic defect should recur in the recipient with a sufficient latency period [137]. The classical indication fulfilling these criteria is familial amyloidotic polyneuropathy (FAP) [138].…”

Section: Domino Transplantationmentioning

confidence: 99%

The European experience

Roels¹,

Rahmel²

2011

Transplant International

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Summary This mini‐review on European experiences with tackling the problem of organ shortage for transplantation was based on a literature review of predominantly European publications dealing with the issue of organ donation from deceased donors. The authors tried to identify the most significant factors that have demonstrated to impact on donation rates from deceased donors and subsequent transplant successes. These factors include legislative measures (national laws and European Directives), optimization of the donation process, use of expanded criteria donors, innovative preservation and surgical techniques, organizational efforts, and improved allocation algorithms.

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Section: Domino Transplantationmentioning

confidence: 99%

The European experience

Roels¹,

Rahmel²

2011

Transplant International

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“…Organ-specific amyloidogenesis may also be increased upon the process of a transplant; in FAP patients who underwent to conventional LT, although the production of the amyloidogenic-mutated TTR is stopped, cardiac amyloidosis can be exacerbated, probably due to enhanced deposition of wild-type TTR on a template of amyloid derived from variant TTR. 25,26 The two major sites of TTR synthesis are the liver and the choroid plexus of the brain that are respectively, the sources of TTR found in the plasma and in the cerebrospinal fluid (CSF). 7 Therefore, the deposited TTR in the PNS of FAP patients may derive from the plasma pool and/or from the CSF pool of the protein.…”

Section: Discussionmentioning

confidence: 99%

Deposition and passage of transthyretin through the blood-nerve barrier in recipients of familial amyloid polyneuropathy livers

Sousa¹,

Ferrão²,

Fernandes³

et al. 2004

Laboratory Investigation

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Familial amyloid polyneuropathy (FAP) is characterized by deposition of mutated transthyretin (TTR) in the peripheral nervous system. Prior to amyloid fibrils, nonfibrillar TTR aggregates are deposited inducing oxidative stress with increased nitration (3-NT). As the major source of TTR is the liver, liver transplantation (LT) is used to halt FAP. Given the shortage of liver donors, domino LT (DLT) using FAP livers is performed. The correlation between TTR deposition in the skin and nerve was tested in biopsies from normal individuals, asymptomatic carriers (FAP 0) and FAP patients; in FAP 0, nonfibrillar TTR was observed both in the skin and nerve in the same individuals; in patients, amyloid was detected in both tissues. The occurrence of amyloidosis in recipients of FAP livers was evaluated 1-7 years after DLT: TTR deposition occurred in the skin 3 years after transplantation either as amyloid or aggregates; in one of the recipients, fibrillar TTR was present in the epineurium 6 years after DLT. Deposits were scarce and 3-NT immunostaining was irrelevant. Nerve biopsies from DLT recipients had no FAP-related neuropathy. Our findings suggest that TTR amyloid formation occurs faster than predicted and that TTR of liver origin can cross the blood-nerve barrier. Recipients of FAP livers should be under surveillance for TTR deposition and tissue damage.

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“…Das Verfahren der sequenziellen (Domino-)Transplantation hat sich in kurzer Zeit durchgesetzt und wird heute weltweit praktiziert [25,69]. Eine Induktion von Amyloidosen wurde bei Empfängern von FAPLebern bisher nicht bekannt [69].…”

Section: Domino-transplantationunclassified

Transthyretinassoziierte hereditäre Amyloidosen

et al. 2002

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Hereditary amyloidoses form a clinically and genetically heterogeneous group of autosomal-dominantly inherited diseases characterized by the ubiquitous extracellular deposit of fibrillary aggregated proteins. Main components of these unsolvable deposits are physiologic proteins that became amyloidogenic through genetically determined conformation changes resulting in an increase in beta-sheet structures. In the vast majority of cases, the offending protein is variant transthyretin (TTR), of which over 80 mutations are known. Among these, substitution of valine by methionine in position 30 (TTR-Met30) is the most commonly encountered. In typical cases, TTR amyloidoses present with polyneuropathy, carpal tunnel syndrome, autonomic insufficiency, cardiomyopathy, and gastrointestinal features, occasionally accompanied by vitreous opacities and renal insufficiency. Rarely, involvement of the leptomeningeal or meningovascular structures dominates the clinical picture. The clinical expression is highly variable, with many atypical manifestations. Asymptomatic mutations have recently been identified. The age of onset varies greatly between early adulthood and old age. Late-onset atypical manifestations and occurrence of asymptomatic carriers render identification of affected family members difficult despite autosomal-dominant inheritance. Orthotopic liver transplantation (OLT) is the only effective therapy available today. This OLT stops progression of the disease, which is otherwise invariably fatal, by removal of the main production site of the amyloidogenic protein. However, cardiac involvement may progress after OLT for unknown reasons. The indication for OLT and its success depend on the grade of cardiovascular and autonomic dysfunction at the time of surgery, age, comorbidity, and type of mutation. Alternative treatment modalities with drugs stabilizing the native tetrameric conformation of TTR, inhibiting fibril formation or breaking beta-sheet structures, are currently being intensively studied.

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Sequential (domino) transplantation of the liver in a transthyretin-50 familial amyloid polyneuropathy

Cited by 16 publications

References 17 publications

The European experience

The European experience

Deposition and passage of transthyretin through the blood-nerve barrier in recipients of familial amyloid polyneuropathy livers

Transthyretinassoziierte hereditäre Amyloidosen

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