Background: We present a patient with late-onset progressive polyneuropathy and a Congo-red positive staining of sural nerve biopsy, where routine immunohistochemical analysis failed to determine the type of amyloid deposited. Since precise determination of the amyloid type has crucial therapeutic implications, we employed our new biochemical micro-techniques, together with molecular biology methods, to characterize the amyloid protein deposited.
Methods: We used a micro-method for extraction of amyloid proteins, amyloid typing by Western blotting, DNA sequencing, and restriction enzyme site analysis.
Results: Our new micro-technique for biochemical analysis of fat aspirate demonstrated transthyretin (TTR) amyloid (ATTR) deposition in the patient's tissue. Sequence analysis of the TTR-encoding DNA identified a single mutation, causing a valine to alanine substitution (V32A).
Conclusions: Although there are approximately 100 known TTR variants associated with peripheral neuropathy, in Israel only one patient with familial amyloid polyneuropathy (FAP), a patient of Ashkenazi origin with ATTR due to an F33I mutation, has been reported so far. Our study identified a second case of ATTR in the Israeli population, this time in a patient of Iranian-Jewish extraction. The study also emphasizes the importance of our new biochemical micro-techniques in elucidating the type of amyloid protein.