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Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Familial AL-amyloidosis in three Italian siblings
A Miliani1, F Bergesio, M Salvadori
1Institute of Internal Medicine IV, University of Firenze, Italy.
Background And Methods:
Familial occurrence of immunoglobulin-related (AL) amyloidosis has occasionally been reported. In this work we describe the concomitance of systemic amyloidosis and monoclonal gammopathy (one case of Waldenström's macroglobulinemia and two cases without multiple myeloma or related diseases) in three Italian siblings, two males and one female.
Results And Conclusions:
All of them showed a common pattern of polyneuropathy to different degrees; two presented a sicca syndrome and one also suffered from nephropathy. Two of them showed the same HLA typing with the same light chain type (k), but had different presenting symptoms. Polyneuropathy and a history of peptic disease in two cases was suggestive of type III familial amyloidotic polyneuropathy (FAP) occurring in the setting of a familial monoclonal component. However, immunohistochemical studies on different tissue specimens using anti-apolipoprotein A1 and anti-transthyretin antibodies were negative. Further screening of DNA samples for transthyretin (TTR) gene mutations was also negative. Clinical and laboratory investigations ruled out reactive or senile amyloidosis and immunohistochemical studies with anti-light chain antibodies on amyloidotic tissue specimens were positive. As a consequence, this family represents a new case of familial AL-amyloidosis.
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