Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation

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 Val30 Met mutation there is a very heterogeneous group of non-Val30 Met 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 Val122 del 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 Val122 del 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.

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant

AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021.The clinical features,therapeutic strategies,and prognoses of all patients were reviewed.RESULTS:Five patients with a mean age of 52.00±7.23y were diagnosed as RAA.These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant.Vitreous opacity was found in all 10 eyes,and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis.The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes(29%),neovascular glaucoma in 2 eyes(29%),and iris neovascularization in 1 eye(14%).Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography(FFA)in this group of cases,and the incidence of the retinal non-perfusion area was 67%.Although no cases of retinal neovascularization were found,the prognosis of visual acuity was not ideal.CONCLUSION:This is the first report of RAA in patients with the TTR Gly83Arg variant.Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients.Thereafter,regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential.And FFA after vitrectomy is very important,which can help ophthalmologists detect RAA earlier and treat it in time.