Blog
Amyloidosis
Covenant Metabolic Specialists Health Library
Covenant Metabolic Specialists
Physician Reviewed
Dec 3, 2025
Amyloidosis is a rare, potentially serious condition in which abnormal protein deposits—called amyloid—build up in organs and tissues, disrupting their normal function. It can affect the heart, kidneys, liver, nerves, and more. Early symptoms are often vague, making diagnosis difficult. But with early detection and proper treatment, damage can be slowed and quality of life preserved.
What is Amyloidosis?
Amyloidosis occurs when misfolded proteins form insoluble clumps (amyloid fibrils) that accumulate in various tissues, impairing how organs work. There are several types, including AL (light chain), ATTR (transthyretin), and AA (inflammatory-related). The type and location of the amyloid deposits determine symptoms, treatment, and prognosis. Left untreated, amyloidosis can lead to multi-organ failure.
Symptoms
Amyloidosis symptoms vary depending on the organ systems involved. Common signs include:
Severe fatigue or weakness
Swelling in legs, ankles, or abdomen
Shortness of breath (especially during activity or when lying flat)
Tingling or numbness in hands and feet (peripheral neuropathy)
Foamy urine (a sign of protein loss from kidneys)
Weight loss with muscle wasting
Bruising, especially around the eyes
Enlarged tongue (macroglossia)
Diarrhea or constipation
Because amyloidosis mimics many other diseases, it’s often missed or misdiagnosed.
Causes
Amyloidosis is caused by the misfolding of specific proteins in the body, which then clump together and resist breakdown.
Common types include:
AL (light chain): Caused by abnormal plasma cells (linked to multiple myeloma)
ATTR (transthyretin):
Wild-type (wtATTR): Associated with aging
Hereditary (hATTR): Genetic mutations affecting transthyretin protein
AA (secondary): Related to chronic inflammation or infection (e.g. rheumatoid arthritis, TB, Crohn’s)
Risk Factors
Risk factors depend on the type of amyloidosis:
AL Amyloidosis:
Plasma cell disorders (e.g., multiple myeloma)
Age > 60
ATTR Amyloidosis:
Age > 70 (wtATTR)
African descent (higher risk for hereditary V122I mutation)
AA Amyloidosis:
Chronic inflammatory diseases (e.g. lupus, RA, IBD)
Long-standing infections (e.g. osteomyelitis, tuberculosis)
Diagnosis
Timely diagnosis is critical but often delayed. Evaluation may include:
Blood and urine tests for abnormal proteins or organ function
Echocardiogram or cardiac MRI (heart involvement)
Nerve conduction studies (neuropathy)
Biopsy of affected tissue or fat pad aspiration, stained with Congo red
Genetic testing if hereditary ATTR is suspected
Serum/urine immunofixation and free light chain assay (AL amyloidosis)
Treatments
Treatment depends on the type and severity of organ involvement.
AL Amyloidosis:
Chemotherapy: Targets plasma cells (e.g. cyclophosphamide, bortezomib, dexamethasone)
Stem cell transplant: In eligible patients
Supportive organ care (diuretics, dialysis, etc.)
ATTR Amyloidosis:
Tafamidis (Vyndaqel): Slows progression in ATTR cardiomyopathy
Patisiran or inotersen: Gene-silencing therapies for hereditary ATTR
Liver transplant: For some hereditary cases
Heart transplant: In advanced cardiac ATTR
AA Amyloidosis:
Treat the underlying inflammatory condition aggressively (e.g., biologics for RA)
Colchicine in cases linked to familial Mediterranean fever
All types benefit from symptom-specific support, including pain management, physical therapy, and nutritional guidance.
Prevention
There is no known way to prevent amyloidosis entirely, but you can reduce your risk or delay progression by:
Managing chronic inflammatory diseases effectively
Treating infections quickly
Screening early if you have a family history of amyloidosis
Monitoring for symptoms if you have multiple myeloma or MGUS
Genetic counseling for high-risk families
Our Take
Amyloidosis may be rare, but it’s real—and often underdiagnosed. At Covenant, we treat every unexplained case of fatigue, neuropathy, or heart failure as a clue, not a coincidence. This condition rewards early suspicion. The earlier we act, the more organ function we preserve—and the more life we protect.
