AL and ATTR Amyloidosis: Diagnosis and Treatment

Introduction to Amyloidosis

AL amyloidosis results from abnormal production of immunoglobulin light chains by bone marrow plasma cells that form amyloid deposits, according to the American College of Cardiology 1, 2
The American College of Cardiology states that ATTR amyloidosis is caused by amyloid deposits made up of transthyretin (TTR) protein 1

The American College of Cardiology notes that lambda isotype occurs in 75-80% of AL amyloidosis cases, kappa isotype in the remaining cases 3
AL amyloidosis is often associated with multiple myeloma (10-15% of patients with multiple myeloma have AL amyloidosis, and 10% of AL amyloidosis cases are associated with multiple myeloma), as reported by the American College of Cardiology 3
The American College of Cardiology states that AL amyloidosis primarily affects the heart and kidneys, causing restrictive cardiomyopathy and proteinuria respectively 3, 2

The American College of Cardiology notes that ATTR amyloidosis occurs in two forms: hereditary (variant) or acquired (wild-type) 1, 4
Hereditary ATTR amyloidosis is caused by mutations in the TTR gene, according to the American College of Cardiology and Circulation 1, 4
The American College of Cardiology states that wild-type ATTR amyloidosis involves normal "wild-type" TTR protein that misfolds due to aging 1

The American College of Cardiology recommends that clinical suspicion for amyloidosis should be raised with unexplained proteinuria, peripheral/autonomic neuropathy, and characteristic organ involvement patterns 3, 4
The diagnostic workup for amyloidosis includes monoclonal protein screening (serum and urine immunofixation, serum free light chain assay), as recommended by the American College of Cardiology and Circulation 3, 4
The American College of Cardiology and Circulation note that cardiac imaging (echocardiography, cardiac MRI, nuclear scintigraphy) and tissue biopsy (endomyocardial, abdominal fat pad, affected organ) with Congo red staining are important diagnostic tools 4

The Blood Cancer Journal states that therapy for AL amyloidosis targets the underlying plasma cell clone 2
The American College of Cardiology notes that early treatment initiation before irreversible organ damage occurs is critical for improving outcomes in both AL and ATTR amyloidosis 2
The American College of Cardiology recommends that both conditions require multidisciplinary management involving cardiologists, hematologists, neurologists, and other specialists 3

AL amyloidosis primarily affects the heart and kidneys, causing restrictive cardiomyopathy and nephrotic-range proteinuria, whereas ATTR amyloidosis predominantly involves the heart and peripheral/autonomic nervous system 5
The American College of Cardiology recommends different treatments for AL and ATTR amyloidosis, with AL requiring chemotherapy or transplant and ATTR requiring targeted therapies like tafamidis 5, 6

Organ involvement patterns differ between AL and ATTR amyloidosis, with AL commonly presenting with organomegaly, which is less typical in ATTR 5
Wild-type ATTR typically affects older adults, while hereditary ATTR can present at younger ages depending on the specific mutation 6
The European Society of Cardiology suggests that monoclonal protein screening, including serum free light chains and immunofixation electrophoresis, is essential for differentiating between AL and ATTR amyloidosis 6

NT-proBNP and troponin are powerful prognostic indicators in both AL and ATTR amyloidosis, according to the American Heart Association 7
Free light chains and kidney function are uniquely prognostic for AL amyloidosis, while kidney function indicates worse prognosis in ATTR amyloidosis 7
The International Society of Amyloidosis recommends chemotherapy targeting the plasma cell clone for AL amyloidosis, while ATTR amyloidosis requires targeted therapies to stabilize or reduce TTR protein 5, 6