Vol 54, No 6 (2020)
Research Paper
Published online: 2020-12-29

open access

Page views 1550
Article views/downloads 1346
Get Citation

Connect on Social Media

Connect on Social Media

Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) in Poland — genetic and clinical presentation

Marta Lipowska1, Hanna Drac1, Dorota Rowczenio2, Janet Gilbertson2, Philip N. Hawkins2, Anetta Lasek-Bal3, Janusz Szewczuk4, Jacek Grzybowski5, Monika Gawor5, Małgorzata Stępień-Wojno6, Maria Franaszczyk7, Joanna Brydak-Godowska8, Renata Śmierciak9, Agnieszka Ptasińska-Perkowska10, Jan Chandoga11, Robert Petrovic11, Anna Kostera-Pruszczyk1
Pubmed: 33373035
Neurol Neurochir Pol 2020;54(6):552-560.

Abstract

Background. Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) is a rare, progressive, hereditary, highly disabling multisystem disorder. ATTR-FAP phenotypes differ according to the type of TTR mutation, geographic region and other as yet unidentified factors. The aim of this study was to establish the clinical and genetic characteristics of Polish patients.

Methods and patients.
Clinical data and necessary examinations were collected from patients diagnosed with ATTR-FAP at the Department of Neurology of Medical University of Warsaw between 1970 and 2019.

Results.
16 patients from eight unrelated families with five different TTR mutations were identified. The family with Val71Ala TTR mutation presented with early onset severe progressive polyneuropathy, with marked visual symptoms in a few patients. The next family with Ile73Val TTR mutation developed symptoms in middle age, and presented with mixed neuropathic and cardiologic phenotype. Four unrelated families were found to have the Phe33Leu TTR mutation with mixed neuropathic and cardiologic phenotype and late onset of symptoms. Other TTR mutations identified were: Val30Met and Asp38Val, both with late onset sensory, motor and autonomic neuropathy.

Conclusion.
Polish ATTR-FAP cases presented with heterogeneity typical for non-endemic areas. Phe33Leu TTR mutation was the most common, found in four unrelated families.

Article available in PDF format

View PDF Download PDF file

References

  1. Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013; 8: 31.
  2. Rowczenio DM, Noor I, Gillmore JD, et al. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014; 35(9): E2403–E2412.
  3. Myers TJ, Kyle RA, Jacobson DR. Familial amyloid with a transthyretin leucine 33 mutation presenting with ascites. Am J Hematol. 1998; 59(3): 249–251, doi: 10.1002/(sici)1096-8652(199811)59:3<249::aid-ajh13>3.0.co;2-b.
  4. Harding J, Skare J, Skinner M. A second transthyretin mutation at position 33 (Leu/Phe) associated with familial amyloidotic polyneuropathy. Biochim Biophys Acta. 1991; 1097(3): 183–186.
  5. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002; 346(23): 1786–1791.
  6. Hagenacker T, Brenck J, Kastrup O. First report of a rare mutation in a Polish patient with painful late-onset transthyretin amyloidosis. J Neurol Sci. 2014; 346(1-2): 331–332.
  7. Niemczyk R, Brydak-Godowska J, Kecik D, et al. Vitreous amyloidosis in two sisters as the indication of transthyretin-related familial form of systemic amyloidosis among liver transplantation candidates. Transplant Proc. 2009; 41(8): 3085–3087.
  8. Benson MD, Turpin JC, Lucotte G, et al. et al.. A transthyretin variant (alanine 71) associated with familial amyloidotic polyneuropathy in a French family. J Med Genet. 1993 Feb;30(2):120-2. PubMed PMID: 8095302; PubMed Central PMCID. : PMCPMC1016267.
  9. Almeida Md, Lopez-Andreu F, Munar-Qués M, et al. Transthyretin ALA 71: a new transthyretin variant in a Spanish family with familial amyloidotic polyneuropathy. Hum Mutat. 1993; 2(5): 420–421.
  10. Haagsma EB, Scheffer H, Altland K, et al. Transthyretin Val71Ala mutation in a Dutch family with familial amyloidotic polyneuropathy. Amyloid. 2000; 7(3): 218–221.
  11. Zambarakji HJ, Charteris DG, Ayliffe W, et al. Vitreous amyloidosis in alanine 71 transthyretin mutation. Br J Ophthalmol. 2005; 89(6): 773–774.
  12. Suan D, Booth DR, Kennedy IH, et al. Vitreal deposits in Val71Ala transthyretin amyloidosis. Intern Med J. 2012; 42(1): 106–108.
  13. Parman Y, Adams D, Obici L, et al. European Network for TTR-FAP (ATTReuNET). Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP. Curr Opin Neurol. 2016; 29 Suppl 1: S3–SS13.
  14. Klaassen STJ, Hazenberg B, Van Ve, et al. ATTR Amyloidosis: development of cardiac symptoms during 6 years of follow up in different ATTR-variants. Orphanet J Rare Dis. 2015; 10(Suppl 1): O18.
  15. Suhr OB, Larsson M, Ericzon BG, et al. FAPWTRʼs investigators. Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry. Transplantation. 2016; 100(2): 373–381.
  16. Booth DR, Gillmore JD, Persey MR, et al. Transthyretin Ile73Val is associated with familial amyloidotic polyneuropathy in a Bangladeshi family. Mutations in brief no. 158. Online. Hum Mutat. 1998;12(2):135. doi: 10.1002/(SICI)1098-100412:2<135::AID-HUMU10>3.0.CO;2-6. PubMed PMID. 1998; 10694917, doi: 10.1002/(SICI)1098-1004(1998)12:2<135::AID-HUMU10>3.0.CO;2-6.
  17. Liao MF, Chang HSA. novel variant mutation of transthyretin Ile73Val-related amyloidotic polyneuropathy in Taiwanese. Acta Neurol Taiwan. 2013 Jun;22(2):87-92. PubMed PMID. ; 24030042.
  18. Ii S, Minnerath S, Ii K, et al. Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations. Neurology. 1991; 41(6): 893–898.
  19. Holmgren G, Hellman U, Jonasson J, et al. A Swedish family with the rare Phe33Leu transthyretin mutation. Amyloid. 2005; 12(3): 189–192.
  20. Chen CH, Huang CW, Lee MJ. A case of familial amyloidotic polyneuropathy with a rare Phe33Leu mutation in the TTR gene. J Formos Med Assoc. 2014; 113(8): 575–576.
  21. Meng LC, Lyu He, Zhang W, et al. Hereditary Transthyretin Amyloidosis in Eight Chinese Families. Chin Med J (Engl). 2015; 128(21): 2902–2905.
  22. Leibou L, Frand J, Sadeh M, et al. Clinical and genetic findings in eight Israeli patients with transthyretin-associated familial amyloid polyneuropathy. Isr Med Assoc J. 2012 Nov;14(11):662-5. PubMed PMID. ; 23240369.
  23. Augustin S, Llige D, Andreu A, et al. Familial amyloidosis in a large Spanish kindred resulting from a D38V mutation in the transthyretin gene. Eur J Clin Invest. 2007; 37(8): 673–678.
  24. Koike H, Tanaka F, Hashimoto R, et al. Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas. J Neurol Neurosurg Psychiatry. 2012; 83(2): 152–158.
  25. Conceição I, González-Duarte A, Obici L, et al. "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016; 21(1): 5–9.
  26. Hellman U, Alarcon F, Lundgren HE, et al. Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population. Amyloid. 2008; 15(3): 181–186.
  27. Mariani LL, Lozeron P, Théaudin M, et al. French Familial Amyloid Polyneuropathies Network (CORNAMYL) Study Group. Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France. Ann Neurol. 2015; 78(6): 901–916.
  28. Luigetti M, Romano A, Di Paolantonio A, et al. Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care. Ther Clin Risk Manag. 2020; 16: 109–123.
  29. Gertz MA, Mauermann ML, Grogan M, et al. Advances in the treatment of hereditary transthyretin amyloidosis: A review. Brain Behav. 2019; 9(9): e01371.



Neurologia i Neurochirurgia Polska