Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 28;12(8):1152.
doi: 10.3390/genes12081152.

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features

Zoltán Pozsonyi  1 , Gergely Peskó  1 , Hedvig Takács  2 , Dorottya Csuka  1 , Viktória Nagy  2 , Ágnes Szilágyi  1 , Lidia Hategan  2 , Balázs Muk  3 , Beáta Csányi  2 , Noémi Nyolczas  4 , Lívia Dézsi  5 , Judit Mária Molnár  6 , Anita Csillik  7 , Katalin Révész  1 , Béla Iványi  8 , Fruzsina Szabó  6 , Krisztián Birtalan  2 , Tamás Masszi  1 , Zsuzsanna Arányi  7 , Róbert Sepp  2
Affiliations

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features

Zoltán Pozsonyi et al. Genes (Basel). .

Abstract

Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv.

Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients.

Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation.

Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

Keywords: ATTRHis88Arg; amyloidosis; heart failure; polyneuropathy; transthyretin; variant.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genetic spectrum of TTR mutations in Hungarian families, expressed in number and percentage of the affected families (n = 23).
Figure 2
Figure 2
A map of Hungary with geographic distribution of different genetic subtypes of ATTRv patients (n = 40). Full symbols represent symptomatic individuals, while empty symbols represent asymptomatic individuals. The four patients with unknown locations are the patients found during literature search.
Figure 3
Figure 3
Number of families identified with ATTRv in recent years (n = 23).
See this image and copyright information in PMC

References

    1. Wechalekar A.D., Gillmore J.D., Hawkins P.N. Systemic amyloidosis. Lancet. 2016;387:2641–2654. doi: 10.1016/S0140-6736(15)01274-X. - DOI - PubMed
    1. Tanskanen M., Peuralinna T., Polvikoski T., Notkola I.L., Sulkava R., Hardy J., Singleton A., Kiuru-Enari S., Paetau A., Tienari P.J., et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann. Med. 2008;40:232–239. doi: 10.1080/07853890701842988. - DOI - PubMed
    1. Maurer M.S., Hanna M., Grogan M., Dispenzieri A., Witteles R., Drachman B., Judge D.P., Lenihan D.J., Gottlieb S.S., Shah S.J., et al. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey) J. Am. Coll. Cardiol. 2016;68:161–172. doi: 10.1016/j.jacc.2016.03.596. - DOI - PMC - PubMed
    1. Benson M.D., Buxbaum J.N., Eisenberg D.S., Merlini G., Saraiva M.J.M., Sekijima Y., Sipe J.D., Westermark P. Amyloid nomenclature 2020: Update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2020;27:217–222. doi: 10.1080/13506129.2020.1835263. - DOI - PubMed
    1. Finsterer J., Iglseder S., Wanschitz J., Topakian R., Löscher W.N., Grisold W. Hereditary transthyretin-related amyloidosis. Acta Neurol. Scand. 2019;139:92–105. doi: 10.1111/ane.13035. - DOI - PubMed

Publication types

Supplementary concepts