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Hereditary transthyretin amyloidosis presenting with prominent autonomic dysfunction
  1. Mary McCullagh1,
  2. Sinead Hughes2,
  3. Adam Canning2,
  4. Seamus Napier3,
  5. Julian Gillmore4,
  6. Mark Owen McCarron1
  1. 1Neurology, Altnagelvin Area Hospital, Derry, UK
  2. 2Cardiology, Altnagelvin Area Hospital, Derry, UK
  3. 3Pathology, Royal Victoria Hospital, Belfast, UK
  4. 4Centre for Amyloid and Acute Phase Proteins Division of Medicine, Royal Free Hospital, London, UK
  1. Correspondence to Dr Mary McCullagh, Neurology, Altnagelvin Area Hospital, Derry, UK; maryt.mccullagh{at}


A 56-year-old man reported 2 years of slowly progressive exertional fatigue, presyncope, paraesthesia, generalised weakness and nocturnal bowel frequency. He had an abnormal Valsalva ratio and significant postural hypotension. Serum N-terminal pro-B-type natriuretic peptide and troponin T were elevated. Transthoracic echocardiogram identified thickening of the biventricular walls, interatrial septum and atrioventricular valve leaflets. Global longitudinal strain was reduced with relative apical sparing, suspicious for cardiac amyloidosis. Technetium-99m and 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy supported a diagnosis of transthyretin amyloidosis (ATTR). However, urinary Bence Jones protein (kappa) was identified despite a normal kappa/lambda light chain ratio and no serum paraprotein. Bone marrow and buccal biopsy provided histological confirmation of amyloid. The bone marrow had no evidence of plasma cell dyscrasia but positive TTR immunohistochemistry. The patient had a T60A genetic mutation for hereditary ATTR. Overlapping cardiac and autonomic symptoms prompt an amyloid workup, which then must distinguish AL amyloid from ATTR pathology.


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  • Contributors MC conceived the idea of the paper, wrote the first draft and revised subsequent drafts. SH contributed to revision of the report. AC helped with imaging and revisions of the report. SN provided pathological imaging and reporting. JG helped manage the patient and contributed to revisions of the report. MOM helped conceive the idea of the paper and revised previous drafts.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JG has consulting income from Ionis, Alexion, Eidos, Intellia, Alnylam and Pfizer.

  • Provenance and peer review Not commissioned; externally peer reviewed by Alex Rossor, London, UK.