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A 55-year-old man with peripheral neuropathy and autonomic dysfunction develops heart failure. His father had similar symptoms and died in his 60s. Genetic testing reveals a TTR mutation.

AD; TTR (transthyretin)

  • Val122Ile common in African Americans
  • Val30Met common in endemic areas (Portugal, Sweden, Japan)
  • Progressive sensorimotor polyneuropathy
  • Cardiomyopathy (restrictive/infiltrative)
  • Autonomic dysfunction (orthostatic hypotension, GI, erectile dysfunction)
  • Vitreous opacities
  • Tissue biopsy shows amyloid with Congo red apple-green birefringence under polarized light; mass spectrometry or immunohistochemistry types the deposit to distinguish ATTR from AL amyloidosis
  • Technetium pyrophosphate (Tc-99m PYP) cardiac scintigraphy is highly sensitive and specific for ATTR cardiac amyloid and can confirm it noninvasively
  • TTR sequencing distinguishes hereditary (variant) ATTR from wild-type, age-related ATTR and enables cascade testing
  • Tafamidis (TTR stabilizer), patisiran/inotersen (TTR silencers), liver transplant (selected cases)

"Trans-thy-retin": The protein name tells you its function: it TRANSports THYroid hormone and RETINol (vitamin A) in the blood. When it misfolds, it forms amyloid deposits in the heart and nerves