Clinical Information

The systemic amyloidoses are a number of disorders of varying etiology characterized by extracellular protein deposition. The most common form is an acquired amyloidosis secondary to multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) in which the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of proteins. There are also hereditary forms of amyloidosis.

The hereditary amyloidoses comprise a group of autosomal dominant, late-onset diseases that show variable penetrance. A number of genes have been associated with hereditary forms of amyloidosis including those that encode transthyretin, apolipoprotein AI, apolipoprotein AII, fibrinogen alpha chain, cystatin C, lysozyme, and gelsolin. Apolipoprotein AI, apolipoprotein AII, lysozyme, and fibrinogen amyloidosis present as non-neuropathic systemic amyloidosis, with renal dysfunction being the most prevalent manifestation.

Gelsolin (GSN) amyloidosis (amyloidosis V) is characterized by corneal lattice dystrophy, cranial neuropathy, and skin changes. Peripheral neuropathy may be present but is typically mild. Like the other hereditary amyloidoses, it is an autosomal dominant disorder; however, homozygosity has been reported and is associated with accelerated renal disease.

Due to the clinical overlap between the acquired and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and consider appropriate therapeutic interventions. Tissue-based, laser capture tandem mass spectrometry might serve as a useful test preceding gene sequencing to better characterize the etiology of the amyloidosis, particularly in cases that are not clear clinically.