Familial Amyloidosis of the Finnish Type: Clinical and Neurophysiological Features of Two Index Cases

Overview

Journal BMJ Case Rep

Specialty General Medicine

Date 2022 Nov 15

PMID 36379630

Authors

Ines Antunes Cunha

Ana Bras

Fatima Silva

Anabela Matos

Affiliations

Soon will be listed here.

Abstract

Familial amyloidosis of the Finnish type (FAF) is a rare multisystemic disorder caused by mutations in the gelsolin gene. The clinical presentation is typically characterised by a triad of ophthalmic, neurological and dermatological findings. FAF has been reported in several countries, primarily in Finland and recently in Portugal. We report the first genetically confirmed cases of FAF from two unrelated families in our neuromuscular outpatient clinic. Gelsolin gene sequencing revealed the heterozygous gelsolin mutation (c.640G>A). The clinical features and the neurophysiological studies of two index patients and their relatives are presented. Obtaining an early diagnosis can be challenging, but FAF should be considered in the differential diagnosis of progressive bilateral facial neuropathy, even if there is no known Finnish ancestor.

References

Cabral-Macias J, Garcia-Montano L, Perezpena-Diazconti M, Aguilar M, Garcia G, Vencedor-Meraz C . Clinical, histopathological, and in silico pathogenicity analyses in a pedigree with familial amyloidosis of the Finnish type (Meretoja syndrome) caused by a novel gelsolin mutation. Mol Vis. 2020; 26:345-354. PMC: 7195602. View

Sagnelli A, Piscosquito G, Bella D, Fadda L, Melzi L, Morico A . Hereditary gelsolin amyloidosis (HGA): a neglected cause of bilateral progressive or recurrent facial palsy. J Peripher Nerv Syst. 2016; 22(1):59-63. DOI: 10.1111/jns.12200. View

Kiuru S, Salonen O, Haltia M . Gelsolin-related spinal and cerebral amyloid angiopathy. Ann Neurol. 1999; 45(3):305-11. DOI: 10.1002/1531-8249(199903)45:3<305::aid-ana5>3.0.co;2-e. View

Hastbacka J, de la Chapelle A, Kaitila I, Sistonen P, Weaver A, LANDER E . Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet. 1992; 2(3):204-11. DOI: 10.1038/ng1192-204. View

Solomon J, Page L, Balch W, Kelly J . Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention. Crit Rev Biochem Mol Biol. 2012; 47(3):282-96. PMC: 3337338. DOI: 10.3109/10409238.2012.661401. View

Conceicao I, Sales-Luis M, de Carvalho M, Evangelista T, Fernandes R, Paunio T . Gelsolin-related familial amyloidosis, Finnish type, in a Portuguese family: clinical and neurophysiological studies. Muscle Nerve. 2003; 28(6):715-21. DOI: 10.1002/mus.10474. View

Sridharan M, Highsmith W, Kurtin P, Zimmermann M, Theis J, Dasari S . A Patient With Hereditary ATTR and a Novel AGel p.Ala578Pro Amyloidosis. Mayo Clin Proc. 2018; 93(11):1678-1682. DOI: 10.1016/j.mayocp.2018.06.016. View

Kiuru-Enari S, Haltia M . Hereditary gelsolin amyloidosis. Handb Clin Neurol. 2013; 115:659-81. DOI: 10.1016/B978-0-444-52902-2.00039-4. View

Carrwik C, Stenevi U . Lattice corneal dystrophy, gelsolin type (Meretoja's syndrome). Acta Ophthalmol. 2009; 87(8):813-9. DOI: 10.1111/j.1755-3768.2009.01686.x. View

10.

Stewart H, Parveen R, Ridgway A, Bonshek R, Black G . Late onset lattice corneal dystrophy with systemic familial amyloidosis, amyloidosis V, in an English family. Br J Ophthalmol. 2000; 84(4):390-4. PMC: 1723421. DOI: 10.1136/bjo.84.4.390. View

11.

Meretoja J . Familial systemic paramyloidosis with lattice dystrophy of the cornea, progressive cranial neuropathy, skin changes and various internal symptoms. A previously unrecognized heritable syndrome. Ann Clin Res. 1969; 1(4):314-24. View

12.

Kiuru S, Seppalainen A . Neuropathy in familial amyloidosis , Finnish type (FAF): electrophysiological studies. Muscle Nerve. 1994; 17(3):299-304. DOI: 10.1002/mus.880170307. View

13.

Alabdali M, Barnett C, Abraham A, Jaafari D, Bril V . Gelsolin Familial Amyloidosis Peripheral Neuropathy in Canada: A Case Report. Can J Neurol Sci. 2015; 42(5):353-5. DOI: 10.1017/cjn.2015.56. View

14.

Solari H, Ventura M, Antecka E, Belfort Junior R, Burnier Jr M . Danish type gelsolin-related amyloidosis in a Brazilian family: case reports. Arq Bras Oftalmol. 2011; 74(4):286-8. DOI: 10.1590/s0004-27492011000400012. View

15.

Lucero Saa F, Cremona F, Minguez N, Igarzabal M, Chiaradia P . The First Argentinian Family with Familial Amyloidosis of the Finnish Type. Case Rep Ophthalmol. 2017; 8(2):446-451. PMC: 5597921. DOI: 10.1159/000479729. View

16.

Benson M, Buxbaum J, Eisenberg D, Merlini G, Saraiva M, Sekijima Y . Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2020; 27(4):217-222. DOI: 10.1080/13506129.2020.1835263. View

17.

Sethi S, Theis J, Quint P, Maierhofer W, Kurtin P, Dogan A . Renal amyloidosis associated with a novel sequence variant of gelsolin. Am J Kidney Dis. 2012; 61(1):161-6. DOI: 10.1053/j.ajkd.2012.07.016. View

18.

Efebera Y, Sturm A, Baack E, Hofmeister C, Satoskar A, Nadasdy T . Novel gelsolin variant as the cause of nephrotic syndrome and renal amyloidosis in a large kindred. Amyloid. 2014; 21(2):110-2. PMC: 4061150. DOI: 10.3109/13506129.2014.891502. View

19.

Meretoja J . Genetic aspects of familial amyloidosis with corneal lattice dystrophy and cranial neuropathy. Clin Genet. 1973; 4(3):173-185. DOI: 10.1111/j.1399-0004.1973.tb01140.x. View

20.

Schmidt E, Mustonen T, Kiuru-Enari S, Kivela T, Atula S . Finnish gelsolin amyloidosis causes significant disease burden but does not affect survival: FIN-GAR phase II study. Orphanet J Rare Dis. 2020; 15(1):19. PMC: 6969418. DOI: 10.1186/s13023-020-1300-5. View