A patient with long-standing type 2 diabetes develops cardiac dysfunction. Autopsy shows extensive amyloid deposits in the cardiac interstitium. Mass spectrometry of the amyloid identifies ATTR (transthyretin) protein. Which fibril form of ATTR is most likely responsible given this clinical context?
- A Mutant ATTR (ATTRm) — hereditary transthyretin amyloidosis with a destabilising missense variant such as Val30Met
- B Wild-type ATTR (ATTRwt) — age-related misfolding of normal transthyretin causing senile systemic amyloidosis predominantly affecting the heart ✓
- C AA amyloid from chronic diabetic inflammation, incorrectly typed by mass spectrometry
- D AL amyloid from plasma cell dyscrasia misidentified as ATTR on spectrometry
Explanation
Wild-type transthyretin (ATTRwt) amyloid, previously called senile systemic amyloidosis, is the most common form of cardiac ATTR amyloidosis in older men. Normal TTR (a transport protein for thyroxine and retinol-binding protein) becomes conformationally unstable with aging and misfolds into amyloid fibrils that preferentially deposit in the cardiac interstitium, causing restrictive cardiomyopathy. It is particularly prevalent in elderly males. Hereditary ATTR (ATTRm) due to specific mutations (e.g., Val30Met causing familial amyloid polyneuropathy, or Val122Ile common in African Americans causing cardiac amyloid) requires genetic testing to distinguish. Mass spectrometry is the gold standard for typing amyloid and would not misidentify ATTR.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.