AL amyloidosis

Amyloidosis is a rare group of disorders with protean manifestations characterized by tissue deposition of misfolded protein. Removal of such deposits is poor, resulting in progressive accumulation of amyloid deposits and disruption of organ function. Among patients with systemic amyloidosis, AL-type protein is more common than AA (secondary amyloidosis), which is caused by chronic infection or chronic inflammatory disease. Familial amyloidoses are rare (estimated incidence <1 per 100,000). They are autosomal dominant inherited diseases with manifestations of amyloid deposition developing in mid-life. The most common form results from mutations in transthyretin protein. This article focuses on AL amyloidosis, formerly known as primary amyloidosis, which most frequently affects the kidneys, heart, liver and peripheral nervous system. Fatigue and weight loss are common, but diagnosis is rarely made until symptoms are referable to a particular organ. Untreated, it is progressive and fatal within 2 years in about 80% of patients. The three-step approach to diagnosis and investigation involves establishing the diagnosis, assessing the extent of organ involvement and excluding plasma cell dyscrasia/lymphoma. Treatment aims to reduce production of amyloidogenic light chains and stabilize organ function. New drugs classes such as proteasome inhibitors (e.g. bortezomib) and immunomodulatory agents (e.g. pomalidomide) show promise in rapidly reducing light-chain burden and halting amyloid production. Current research focuses on reducing amyloid load by interfering with protein misfolding and interaction with serum amyloid P protein.