Hereditary amyloidosis

Our experience with 465 patients with sporadic, biopsy-proven, systemic amyloidosis indicates that immunoelectron-microscopical typing of amyloid deposits improves diagnostic accuracy and optimizes DNA analysis.3 The diagnosis of AL amyloidosis must not be presumed, and no patient should receive chemotherapy for a monoclonal disorder if the diagnosis has not been verified.4 Monoclonality was documented by high-resolution immunofixation5 in 96 percent of 446 patients who ultimately received a diagnosis of primary amyloidosis and by immunoelectron microscopy in the remaining 4 percent. Since the presence of a monoclonal protein supports, but does not prove, the diagnosis of AL amyloidosis, we used immunoelectron microscopy to type the amyloid deposits in 134 consecutive patients with sporadic systemic amyloidosis who presented with a monoclonal protein. The diagnosis of AL amyloidosis was established in 129 patients, all of whom had a clinical presentation consistent with the diagnosis. Among five patients with a questionable history or presentation, amyloid typing disclosed AL amyloid in two patients, transthyretin in two, and apolipoprotein A-I in one. We found that ultrastructural immunohistochemical analysis unambiguously characterized the amyloid deposits, by colocalizing the specific protein with the fibrils, in all 37 patients (8 percent) who had sporadic amyloidosis without a monoclonal protein. It allowed typing of κ and λ light-chain deposits in all instances, whereas traditional immunohistochemical analysis was positive in only 38 percent of patients.1 The variable penetrance of the genetic defects indicates the need for confirmation by tissue typing. It seems more cost effective to focus the DNA analysis on specific genes by first typing the amyloid deposits with the use of ultrastructural immunohistochemical techniques.