amyloidose

Amyloidosis, or amyloidose, refers to a group of diseases in which misfolded proteins aggregate into insoluble beta-pleated fibrils that deposit extracellularly in tissues and organs. The resulting tissue damage can impair organ function and lead to a range of clinical problems. Amyloidosis is broadly categorized as systemic, with multi-organ involvement, or localized, confined to a single tissue or site.

The systemic forms are the most clinically important. The most common types are AL (light-chain) amyloidosis, caused by a clonal population of plasma cells producing abnormal light chains; AA (secondary) amyloidosis, related to chronic inflammatory or infectious diseases; and hereditary or wild-type transthyretin-related (ATTR) amyloidosis, due to abnormal transthyretin protein produced by the liver or by age-related deposition. Other causes include dialysis-related amyloidosis due to beta-2 microglobulin deposition. Localized amyloidosis involves deposition of the same or different amyloid proteins in a single organ without systemic spread.

Clinical features depend on the organs affected and may include proteinuria and kidney dysfunction, restrictive cardiomyopathy or arrhythmias, peripheral and autonomic neuropathy, hepatomegaly, tongue enlargement, and gastrointestinal or cutaneous symptoms. Because symptoms are diverse, diagnosis requires tissue biopsy with Congo red staining showing apple-green birefringence under polarized light, followed by typing by immunohistochemistry or mass spectrometry. Laboratory tests such as serum and urine protein electrophoresis with immunofixation and measurement of serum free light chains aid in identifying AL amyloidosis; imaging and organ function assessment guide evaluation of organ involvement.

Treatment aims to reduce precursor protein production and manage organ dysfunction. AL amyloidosis is treated with plasma cell-directed therapy; AA amyloidosis focuses on controlling the underlying inflammatory disease; ATTR amyloidosis employs TTR stabilizers or gene-silencing therapies and supportive care. Prognosis varies widely by type and extent of organ involvement.