Background

Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils (i.e. amyloid). Apart from the common Val30Met mutation there is a very heterogeneous group of non-Val30Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy.

Methods

A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed.

Results

Three patients needed a staged (1 patient) or simultaneous (2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac (allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months.

Conclusions

This is the first report in (liver) transplant literature about the rare Val122del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

中文翻译：

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有症状的 Val122del 突变遗传性转甲状腺素蛋白淀粉样变性：需要早期诊断和优先考虑心脏和肝脏移植

背景

遗传性转甲状腺素蛋白 (ATTRv) 淀粉样变性是一种常染色体显性遗传疾病，与转甲状腺素蛋白基因突变相关，导致转甲状腺素蛋白四聚体不稳定。在解离和错误折叠后，它们重新组装成不溶性原纤维（即淀粉样蛋白）。除了常见的 Val30Met 突变外，还有一组非常异质的非 Val30Met 突变。在某些情况下，临床表现主要是快速发展的限制性和肥厚型心肌病。

方法

介绍了具有高度临床相关性、罕见且特别具有侵袭性的 Val122del 突变的四名肝脏受者的病例系列。讨论了内科和外科治疗选择、ATTRv-淀粉样变性的等候名单政策，包括心脏移植的需要，以及心肝移植的现状。

结果

由于快速进展的心力衰竭和/或神经功能障碍，三名患者需要分期（1 名患者）或同时（2 名患者）心肝移植。由于心肌病引起的肝纤维化转化，2人无法进行多米诺肝移植。经过 3.5 至 9.5 年的随访，所有患者的心脏（同种异体移植物）功能均得以维持，但 3 例患者出现神经病变，其中 1 例在 80 个月后死亡。

结论

这是（肝）移植文献中关于罕见的 Val122del ATTRv 突变的第一篇报道。由于其侵袭性，有症状的患者应优先考虑肝脏，如果患有心肌病，则应优先考虑心脏等待名单，以避免导致快速致命结果的不可逆转的神经和心脏损伤。