Skill Checkup: An Electrical Conundrum

Xiaoxiao Qian, MD; Raghav Gattani, MD; Chirag M. Sandesara, MD


June 11, 2021

Serum free light chains and serum and urine immunofixation electrophoresis are very sensitive for AL amyloidosis. This patient had a serum kappa/lambda free light chain ratio > 1.65 and significantly elevated serum and urine monoclonal proteins. In the setting of his presentation and comorbidities, the most likely diagnosis is AL amyloidosis. Serum and urine electrophoresis testing is less sensitive than immunofixation electrophoresis and should be avoided.

Hereditary ATT-related (hATTR) amyloidosis is a mutation in the transthyretin (TTR) gene located on chromosome 18 that causes misfolding of the TTR protein and deposition of transthyretin amyloid fibrils in multiple organs and tissues in the body. Transthyretin is synthesized mainly in the liver and normally functions as a transporter of thyroxine and retinol. hATTR amyloidosis is a progressive disease that has heterogeneous clinical manifestations, most commonly polyneuropathy and cardiomyopathy. Features of the disease depend on the variant and include autonomic neuropathy (orthostatic hypotension), cardiac dysfunction (conduction system abnormalities, cardiomyopathy, arrhythmia), gastrointestinal dysfunction (alternating symptoms of diarrhea and constipation, and unintentional weight loss), ocular manifestations (vitreous opacity, or glaucoma), renal dysfunction, or carpal tunnel syndrome. Cardiac ATTR typically manifests with HFpEF, right-sided congestive heart failure, cardiomegaly, and conduction system aberrations.

Wild-type (wt) transthyretin accumulates in tissues and causes wt-ATTR cardiac amyloidosis, which is a form of amyloidosis associated with aging (formerly called "senile secondary amyloidosis"). ATTR-wt cardiac amyloidosis presents as HFpEF in men older than 70 years. Peripheral edema, atrial fibrillation, and carpal tunnel syndrome are common features. Familial amyloid cardiomyopathy is the disease variant where the heart is involved and the nervous tissue spared; when the reverse occurs, the disease is termed "familial amyloidotic polyneuropathy."[2]

Patients with hATTR and wt-ATTR amyloidosis have normal findings on serum and urine immunofixation electrophoresis. Bone scintigraphy is diagnostic for ATTR cardiac amyloidosis, as discussed in Question 2.

Serum and urine free light chain concentrations can be elevated in multiple myeloma; however, multiple myeloma does not cause infiltrative heart disease. Patients with multiple myeloma can have heart failure, but it is usually high-output heart failure, most likely related to an arteriovenous fistula at the level of bone marrow. This patient also had a bone marrow biopsy, which demonstrated plasma cell dyscrasia and positive Congo Red staining, also corroborating the diagnosis of AL amyloidosis.


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