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Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)

INTRODUCTION

Amyloidosis is a generic term that refers to the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of normal serum proteins. These fibrils have a predominantly antiparallel ß-pleated sheet configuration (noted on x-ray diffraction), and can be identified on biopsy specimens both by their characteristic appearance on electron microscopy, and by their ability to bind Congo red (leading to green birefringence under polarized light) and thioflavine T (producing an intense yellow-green fluorescence).

More than 20 distinct low molecular weight proteins are recognized to form amyloid fibrils. The two most common causes of systemic amyloid deposition are:

Immunoglobulin light chain (AL) amyloidosis (previously referred to as primary amyloidosis) in which the fibrils are composed of fragments of monoclonal light chains. Affected patients may have amyloidosis alone or in association with other plasma cell dyscrasias (multiple myeloma, Waldenstrom macroglobulinemia). All forms of systemic amyloidosis in which the fibrils are derived from monoclonal light chains, regardless of the nature of the underlying plasma cell disorder (eg, MGUS, multiple myeloma, or Waldenstrom macroglobulinemia) are considered AL amyloidosis.

AA amyloidosis in which the fibrils are composed of fragments of the acute phase reactant serum amyloid A. AA amyloidosis is typically reactive (secondary) to chronic inflammation. (See "Pathogenesis of secondary (AA) amyloidosis".)

AL amyloidosis is a systemic disorder that can present with a variety of symptoms or signs, including heavy proteinuria (usually in the nephrotic range), edema, hepatosplenomegaly, otherwise unexplained heart failure, and the carpal tunnel syndrome. Although virtually all patients have multisystem amyloid deposition, it is not uncommon to present with evidence of mainly one organ being affected. (See "Renal amyloidosis" and "Gastrointestinal amyloidosis" and "Clinical manifestations and diagnosis of amyloid cardiomyopathy".)

                            

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Literature review current through: Sep 2014. | This topic last updated: May 29, 2014.
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