Case of the Month #56 The Protein Puzzle: A Case of Progressive Multi-Organ Dysfunction

Diagnostic confirmation requires:

1. Clinical suspicion based on multi-system involvement
   • Heart failure with preserved ejection fraction
   • Nephrotic syndrome
   • Peripheral/autonomic neuropathy
   • Macroglossia, periorbital purpura
   • Carpal tunnel syndrome
2. Laboratory investigations
   • Serum     and     urine     protein     electrophoresis               and immunofixation
   • Serum free light chain assay (kappa, lambda, and ratio)
   • NT-proBNP and cardiac troponins
   • Proteinuria quantification
3. Imaging
   • Echocardiography: increased ventricular wall thickness, "speckled" appearance, restrictive filling pattern
   • Cardiac      MRI:      characteristic      late                   gadolinium enhancement pattern, abnormal myocardial nulling
   • Nuclear scintigraphy: high uptake of bone tracers in cardiac ATTR amyloidosis
4. Tissue diagnosis (gold standard)
   • Congo red staining with apple-green birefringence under polarized light
   • Laser microdissection with mass spectrometry to type the amyloid protein
   • Common biopsy sites: abdominal fat pad, bone marrow, affected organ (e.g., heart, kidney)