Amyloidosis

Amyloidosis is a group of protein misfolding diseases in which normally soluble proteins aggregate into insoluble amyloid fibrils that deposit in tissues, disrupting organ structure and function. The clinician recognizes the major clinical subtypes: AL (primary/light chain) amyloidosis -- the most common systemic form, caused by clonal plasma cell proliferation producing misfolded immunoglobulin light chains (lambda more common than kappa) that deposit in the heart, kidneys, liver, nerves, and soft tissues; AA (secondary) amyloidosis -- serum amyloid A protein deposits resulting from chronic inflammatory conditions (rheumatoid arthritis, inflammatory bowel disease, chronic infections, familial Mediterranean fever); ATTR (transthyretin) amyloidosis -- wild-type (senile cardiac amyloidosis, increasingly recognized in elderly men with HFpEF) or hereditary (autosomal dominant TTR gene mutations). Clinical manifestations depend on organ involvement: cardiac (restrictive cardiomyopathy with wall thickening, diastolic dysfunction, characteristic granular sparkling on echocardiography, low-voltage QRS on ECG despite thick walls -- a classic discordance), renal (proteinuria progressing to nephrotic syndrome), neurological (peripheral neuropathy, autonomic dysfunction with orthostatic hypotension), hepatic (hepatomegaly, elevated alkaline phosphatase), and soft tissue (macroglossia, periorbital purpura -- pathognomonic for AL). Diagnosis: tissue biopsy with...