Ostertag revisited: The inherited systemic amyloidoses without neuropathy

Abstract

Mutations in a number of plasma proteins, including transthyretin, apolipoprotein AI, fibrinogen Aα-chain, lysozyme, and apolipoprotein AII, are associated with hereditary systemic amyloidosis. Transthyretin amyloidosis is the most common and is usually associated with peripheral neuropathy. Mutations in the other proteins usually have no neuropathic consequences and, instead, cause principally renal and cardiac amyloidosis. Only the apolipoprotein AI glycine 26 arginine mutation may cause peripheral neuropathy and then in only some of the kindreds with this disease. This review is concerned with the non-neuropathic hereditary systemic amyloidoses. It strives to present a synopsis of the present day knowledge of these diseases including each feature of each precursor protein and its mutations; the clinical phenotype of the disease; and suggestions for treatment when feasible. The main objective is to increase awareness of these autosomal dominant diseases, enhance the chances of early diagnosis, enhance the physician's and subsequently the patient's knowledge of each disease, and finally emphasize the need for more research to find ways to treat or prevent these diseases.

• Hereditary
• familial
• amyloidosis
• amyloid

SSCP = single strand conformation polymorphism; RFLP = restriction fragment length polymorphism; Apo AI = apolipoprotein AI; Apo AII = apolipoprotein AII; Lys = lysozyme; FibAα = fibrinogen Aα chain; PCR = polymerase chain reaction

SSCP = single strand conformation polymorphism; RFLP = restriction fragment length polymorphism; Apo AI = apolipoprotein AI; Apo AII = apolipoprotein AII; Lys = lysozyme; FibAα = fibrinogen Aα chain; PCR = polymerase chain reaction