Gelsolin amyloidosis : from genealogy to clinical features

Tuuli Mustonen

Tutkimustuotos: OpinnäyteVäitöskirjaArtikkelikokoelma


Amyloid diseases, in general, cause formation and deposition of insoluble amyloid fibrils either locally or systemically, disrupting normal organ function. Gelsolin amyloidosis is an autosomal dominantly inherited amyloidosis in which a point mutation in the gelsolin gene results in systemic deposition of gelsolin-derived amyloid. Gelsolin amyloidosis belongs to the Finnish disease heritage, and patients are thus primarily observed in Finland. Only the c.640G>A major mutation has been detected to date in Finland, but worldwide also rarer disease-causing gelsolin gene point mutations have been found. The disease manifests generally as progressive ophthalmological, neurological, and cutaneous symptoms. The aim of this study was to extend knowledge on the genetic background and clinical features of gelsolin amyloidosis. This study aimed to determine whether all the Finnish gelsolin amyloidosis patients descend from the same common ancestor or whether sporadic mutations have taken place. The clinical picture, prevalence of different symptoms, clinical course, and sex differences were of interest. One of the targets was also to identify rarer, possibly disease-related symptoms. Individual clinical studies were designed to clarify cardiac manifestations and hearing ability in gelsolin amyloidosis patients. A Finnish national patient registry was founded, and information on symptoms and disease course in addition to genealogic data was inquired. The data were complemented by medical records and telephone interviews. The genetic background was evaluated by means of classical genealogy and haplotype analysis. Data in the cardiac study were collected through clinical examinations, electrocardiograms, and cardiac magnetic resonance imaging. Hearing abilities were examined by automatic pure tone audiometry and speech-in-noise test, in addition to clinical examinations and standardized hearing evaluating questionnaires. Altogether 79 gelsolin amyloidosis families were identified. The same c.640G>A mutation-associated haplotype, uncommon in the general Finnish population, was demonstrated in all of the 62 families investigated. In total, information on 227 patients was gathered in the registry. The first symptoms were reported on average at the age of 40 years, followed by neurological and cutaneous symptoms. Eye-related symptoms seemed to be more severe in women who also reported symptoms on average four years earlier than men. In addition to well-known symptoms, cardiac pacemakers were observed in 4% and atrioventricular or intraventricular conduction disorders in 43% of patients. Impaired hearing was commonly reported (40% of patients), but subsequent hearing evaluations did not indicate any disease-related impaired hearing. The study strongly indicated that all Finnish gelsolin amyloidosis patients share a common ancestor. Knowledge of the prevalence of ophthalmological, neurological, and cutaneous symptoms increased. The study indicated that eye-related problems may be somewhat more severe in women, although no major sex differences were seen. Earlier suspicions of disease-related conduction disorders were strengthened. On the other hand, hearing impairment does not seem to be one of the clinical features, contradicting the previous literature.
  • Atula, Sari, Valvoja
  • Kiuru-Enari, Sari Maaret Kristiina, Valvoja
Painoksen ISBN978-951-51-8465-8
Sähköinen ISBN978-951-51-8466-5
TilaJulkaistu - 2022
OKM-julkaisutyyppiG5 Tohtorinväitöskirja (artikkeli)


M1 - 113 s. + liitteet


  • 3112 Neurotieteet
  • 3124 Neurologia ja psykiatria
  • 1184 Genetiikka, kehitysbiologia, fysiologia

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