endocrine and metabolic disorders
Amyloidosis
Key Points
Amyloidosis is a group of disorders in which certain misfolded proteins aggregate into insoluble fibrils that are deposited within organs, causing dysfunction. Many different proteins are prone to misfold; some of these proteins are produced by a genetic defect or by certain disease states, whereas others involve immunoglobulin light chains produced by monoclonal plasma cell or other B-cell lymphoproliferative disorders. The amyloidogenic protein determines the amyloid type and clinical course of disease, although the clinical manifestations of the different types may overlap. Many organs can be affected, but cardiac involvement carries a particularly poor prognosis; amyloid cardiomyopathy typically leads to diastolic dysfunction, heart failure, and heart block or arrhythmia. Diagnosis is by biopsy; type of amyloidosis is determined by a variety of immunologic, genetic, and biochemical tests. Mass spectrometry is the most sensitive and specific method for amyloid typing. Appropriate supportive care will help relieve symptoms and improve quality of life; organ transplantation can help selected patients. Treat the underlying process; for AL amyloidosis due to plasma cell or lymphoproliferative disorders, chemotherapy can be highly effective; for secondary AA amyloidosis, anti-infectious and anti-inflammatory drugs can help. For hereditary ATTR amyloidosis, small molecule stabilizer therapeutics and gene-silencing medications inhibit or potentially reverse neurologic deterioration; for patients with amyloid cardiomyopathy (ATTR or ATTRwt),tafamidisdecreases all-cause mortality and cardiovascular-related hospitalizations. 