Urban Hellman1, Hans-Erik Lundgren2, Per Westermark3, Christina Stafberg4, Hareth Nahi5, Sascha Tachlinski6, Michael Guggi7, Max Flogegård8, Mehmet Hamid9, Stefan A Escher10, Ole B Suhr11. 1. Cardiology, Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 2. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 4. Department of Medicine, Enköpings Lasarett, Enköping, Sweden. 5. Department of Haematology, Karolinska University Hospital, Huddinge, Sweden. 6. Department of Medicine, Mora Lasarett, Mora, Sweden. 7. Department of Cardiology, Falu Lasarett, Falun, Sweden. 8. Department of Medicine, Falu Lasarett, Falun, Sweden. 9. Department of Cardiology, Mälarsjukhuset, Eskildtuna, Sweden. 10. Department of Clinical Science, Genetic & Molecular Epidemiology Unit, Lund University, Malmö, Sweden. 11. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. Electronic address: ole.suhr@umu.se.
Abstract
UNLABELLED: In 2005 we reported the first case of transthyretin His88Arg (p. His108Arg) amyloidosis, a mutation characterised by cardiomyopathy. Six additional gene carriers of whom five have clinical symptoms of disease have now been identified in Sweden, and we have been able to identify a possible founder and to characterise the Swedish phenotype of the transthyretin (TTR) His88Arg mutation. Genealogical studies of church records were used to identify the individuals with the disease and their families. Routine clinical investigations of neurological and heart manifestation of the disease were utilised. We found that genealogically all seven individuals were related and originated from the same region in Sweden. Amyloid deposits were demonstrated in biopsies and the TTR His88Arg mutation was identified in all patients. Patients had a late onset disease (≥ 50 years of age) and all exhibited a severe amyloid cardiomyopathy. A pronounced peripheral axonal neuropathy was with certainty demonstrated in one patient only, who also was operated for a magnetic resonance confirmed spinal stenosis, however, without any effect on his neurological symptoms. Five of the patients had carpal tunnel syndrome. The first reported case is now deceased from cardiac failure. One patient has had a sequential heart and liver transplantation. One gene carrier had no symptoms or findings of disease on latest evaluation at the age of 44. IN CONCLUSION: the Swedish TTRHis88Arg patients all have a common Swedish founder. Cardiomyopathy with heart failure, as well as carpal tunnel syndrome and spinal stenosis were early signs of disease; but peripheral neuropathy was present in one patient before symptoms of cardiomyopathy so the phenotypical presentation of this mutation is variable.
UNLABELLED: In 2005 we reported the first case of transthyretin His88Arg (p. His108Arg) amyloidosis, a mutation characterised by cardiomyopathy. Six additional gene carriers of whom five have clinical symptoms of disease have now been identified in Sweden, and we have been able to identify a possible founder and to characterise the Swedish phenotype of the transthyretin (TTR) His88Arg mutation. Genealogical studies of church records were used to identify the individuals with the disease and their families. Routine clinical investigations of neurological and heart manifestation of the disease were utilised. We found that genealogically all seven individuals were related and originated from the same region in Sweden. Amyloid deposits were demonstrated in biopsies and the TTRHis88Arg mutation was identified in all patients. Patients had a late onset disease (≥ 50 years of age) and all exhibited a severe amyloid cardiomyopathy. A pronounced peripheral axonal neuropathy was with certainty demonstrated in one patient only, who also was operated for a magnetic resonance confirmed spinal stenosis, however, without any effect on his neurological symptoms. Five of the patients had carpal tunnel syndrome. The first reported case is now deceased from cardiac failure. One patient has had a sequential heart and liver transplantation. One gene carrier had no symptoms or findings of disease on latest evaluation at the age of 44. IN CONCLUSION: the Swedish TTRHis88Argpatients all have a common Swedish founder. Cardiomyopathy with heart failure, as well as carpal tunnel syndrome and spinal stenosis were early signs of disease; but peripheral neuropathy was present in one patient before symptoms of cardiomyopathy so the phenotypical presentation of this mutation is variable.