Late onset cardiomyopathy as presenting sign of ATTR A45G amyloidosis caused by a novel TTR mutation (p.A65G)Klaassen, S. H. C., Lemmink, H. H., Bijzet, J., Glaudemans, A. W. J. M., Bos, R., Plattel, W., van den Berg, M. P., Slart, R. H. J. A., Nienhuis, H. L. A., van Veldhuisen, D. J. & Hazenberg, B. P. C., Aug-2017, In : Cardiovascular Pathology. 29, p. 19-22 4 p.
Research output: Contribution to journal › Article › Academic › peer-review
Objective: The clinical description of a novel TTR genemutation characterized by a late onset amyloid cardiomyopathy.
Methods and Results: A 78-year-old man of Dutch origin with recent surgeryforbilateral carpal tunnel syndrome(CTS) was admitted to our hospital because of heart failure with preserved ejection fraction (55%). Cardiac ultrasound showed thickened biventricular walls, and cardiac magnetic resonance imaging also showed late gadolinium enhancement. Early signs of a polyneuropathy were found by neurophysiological testing. A few months later, his 72year- old sister was admitted to an affiliated hospital because of heart failure caused by a restrictive cardiomyopathy. In both patients, a subcutaneous abdominal fat aspirate was stained with Congo red and DNA was analyzed by direct sequencing of exons 1 to 4 of the transthyretin (TTR) gene. Both fat aspirates revealed transthyretin-derived (ATTR) amyloid. Tc-99m-diphosphonate scintigraphy further confirmed cardiac ATTR amyloidosis in the male patient. DNA analysis of both patients showed a novel TTR mutation c.194C>G that encodes for the gene product TTR (p.A65G) ending up as themature protein TTR A45G. The 56-year-old daughter of themale patient had the same TTR mutation. A full diagnostic workup did not reveal any signs of amyloidosis yet.
Conclusions: A novel amyloidogenic TTRmutation was found in a Dutch family. The clinical presentation of ATTR A45G amyloidosis in the affected family members was heart failure due to a late-onset cardiomyopathy. The systemic nature of this disease was reflected by bilateral CTS and by early signs of a polyneuropathy in the index patient.
|Number of pages||4|
|Publication status||Published - Aug-2017|
- ATTR A45G Amyloidosis, Transthyretin, Cardiomyopathy, CTS, PRESERVED EJECTION FRACTION, TRANSTHYRETIN AMYLOIDOSIS, HEART-FAILURE, DIAGNOSTIC PERFORMANCE, FAT TISSUE, POLYNEUROPATHY, GUIDELINES, TAFAMIDIS, VARIANTS, DISEASE