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![]() AA can develop in association with hereditary auto-inflammatory diseases, both monogenic (familial Mediterranean fever) as well as polygenic, including inflammatory bowel disease. AA is typically associated with an underlying chronic inflammatory process and remains the leading cause of systemic amyloidosis in developing countries, due to the high prevalence of associated, underlying, infectious diseases. In AA amyloidosis, amyloid fibrils are derived from serum amyloid A protein, which is an acute phase reactant produced by the liver. ![]() The designation ATTRwt is frequently used to underscore the association with wild-type protein in contrast to the variant. Moreover, “hereditary ATTRv,” where “v” stands for variant instead of “m” for mutant, is recommended by the ISA however, at times, ATTRm (or hATTR for hereditary ATTR) may be encountered in the literature as an alternative to ATTRv. The name “hereditary” rather than “familial” is recommended by the ISA for amyloid diseases associated with mutant proteins. While the single-letter amino acid code is recommended by the ISA, frequently, the three-letter amino acid designation is used in the literature, in keeping with the recommendations of the Sequence Variant Description Working Group of the Human Genome Variation Society. Amyloid protein variants associated with hereditary amyloidoses are named according to the substitution or deletion in the mature protein thus, the name of the amino acid involved and the position of the change are listed: e.g., ATTRV30M (valine is replaced by methionine). Table 1 provides an abbreviated list of amyloid fibril proteins and their precursors in humans. The amyloid is termed A (for amyloid) followed by an abbreviation of the protein type: AL (amyloid derived from immunoglobulin light chain), ATTR (amyloid derived from transthyretin), etc. The current classification of amyloid in medical practice is based on the amyloid protein type. (4) While the spectrum of amyloidoses continues to expand, it is critical to distinguish between those that are currently treatable versus those that are untreatable and avoid causing harm by inappropriate treatment. (3) While mass spectrometry has emerged as the preferred method of amyloid typing, careful application of immune methods is still clinically useful but caution and experience, as well as awareness of the limitations of each method, are necessary in their interpretation. (2) Determination of the protein type is imperative before specific therapy can be implemented. Key Messages: (1) Early diagnosis of amyloidosis continues to pose a significant challenge and requires the participation of many clinical and laboratory specialties. A brief overview of the target organ involvement by amyloid type is also included. Determination of the amyloid protein type is imperative before specific therapy can be implemented and the current methods are briefly summarized. In a dialysis setting, systemic amyloid derived from β 2 microglobulin (Aβ2M) should be considered, although a very rare hereditary variant has also been reported several amyloidoses may be typically associated with aging and several iatrogenic types have also emerged. Other hereditary amyloidoses include AFib, several amyloidoses derived from apolipoproteins, AGel, ALys, etc. The latter is emerging as an underdiagnosed type in both the hereditary and wild-type setting. Among the systemic amyloidoses, AL continues to be the most common amyloid diagnosis in the developed world other clinically significant types include AA, ALECT2, and ATTR. ![]() Moreover, amyloidoses with a genetic component must be distinguished from the sporadic types and systemic amyloidoses must be distinguished from the localized forms. Summary: in clinical practice, it is critical to distinguish between treatable versus non-treatable amyloidoses. To date, 36 proteins have been identified as being amyloidogenic in humans. ![]() Current classification of amyloid in medical practice is based on the amyloid protein type. The deposits are mainly extracellular and are recognizable by their affinity for Congo red and their yellow-green birefringence under polarized light. Background: The amyloidoses are a rare and heterogeneous group of disorders that are characterized by the deposition of abnormally folded proteins in tissues ultimately leading to organ damage.
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