Rare, Underserved, and Underdiagnosed



Amyloidosis is a disorder caused by proteins that possess abnormal conformational features leading them to aggregate and infiltrate tissues in the form of amyloid fibrils. Systemic amyloidosis is a disease that can damage the heart, kidneys, liver, soft tissue and nervous system, resulting in multi-organ failure and death.

Systemic light-chain or AL amyloidosis is associated with B-cell malignancies, usually clonal plasma cell gammopathies that produce immunoglobulin light chains capable of forming amyloid. In addition to depositing as amyloid fibrils, misfolded and aggregated light chains are often toxic to organs; hence, the level of symptoms patients may experience is severe. 

Other types of systemic amyloidosis that are not related to immunoglobulin light chains or B-cell malignancies include the transthyretin-related variants. Mutant transthyretin frequently causes hereditary amyloidosis while wild-type transthyretin (TTR) can cause an age-related disease. All types can cause restrictive cardiomyopathies although the tempo of disease is fastest in AL.

The tools for diagnosing and typing amyloidosis and its treatments have improved significantly over the past 20 years. Advances in therapy for AL have followed those in multiple myeloma, as awareness of the association between AL and clonal plasma cell diseases has increased. In addition, novel therapies to halt or reverse light chain organ damage, as well as treatments for TTR amyloidosis, are in development and clinical testing.

For the physician caring for amyloid patients, common challenges include: the need for expedited diagnosis and typing; the necessity of prompt therapy; the importance of patient and family education; and real-time clinical management of a complex multi system disease. Progress in the field is impeded because of lack of awareness of these rare diseases, the lack of funding to support research in amyloidosis and the challenges in recruiting patients to clinical trials.

Awareness and understanding of these diseases is the first step to delivering better outcomes for patients.