HOW TO DIAGNOSE

Understand the key symptoms that raise clinical suspicion of polyneuropathy1

hATTR-PN is a rapidly progressive and fatal disease that requires urgent identification2,3

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Identification and differentiation of common neuropathies3,7-24

Legend

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Common characteristic

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Possible characteristic

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Not characteristic

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  hATTR-PN Diabetic neuropathy* CIDP† Idiopathic axonal PN
Polyneuropathy manifestations  
Sensory neuropathy common-characteristic-icon common-characteristic-icon common-characteristic-icon common-characteristic-icon
Motor neuropathy common-characteristic-icon‡ possible-characteristic-icon common-characteristic-icon common-characteristic-icon
Autonomic neuropathy common-characteristic-icon possible-characteristic-icon not-characteristic-icon not-characteristic-icon
GI symptoms§ common-characteristic-icon possible-characteristic-icon not-characteristic-icon not-characteristic-icon
EMG/NCS findings  
Axonal damage common-characteristic-icon common-characteristic-icon possible-characteristic-icon common-characteristic-icon
Reduced SNAP amplitude common-characteristic-icon common-characteristic-icon possible-characteristic-icon common-characteristic-icon
Slowed conduction velocity common-characteristic-icon possible-characteristic-icon common-characteristic-icon possible-characteristic-icon
Other involved systems  
Cardiac (HFpEF, Afib) possible-characteristic-icon possible-characteristic-icon not-characteristic-icon not-characteristic-icon
Nephropathy possible-characteristic-icon possible-characteristic-icon not-characteristic-icon not-characteristic-icon
Bilateral carpal tunnel syndrome possible-characteristic-icon|| possible-characteristic-icon not-characteristic-icon not-characteristic-icon
Spinal stenosis possible-characteristic-icon possible-characteristic-icon not-characteristic-icon not-characteristic-icon
Additional clinical features  
Speed of progression Relatively rapid (months) Gradual (years) Progressive/relapsing-remitting pattern (develops over ≥8 weeks) Gradual (years)
Family history possible-characteristic-icon possible-characteristic-icon not-characteristic-icon not-characteristic-icon
Distribution Symmetrical, length dependent, distal (occasionally proximal) Distal (“glove and stocking”) Symmetric proximal and distal, upper and lower limbs Symmetric distal

Genetic testing is critical to confirm a diagnosis of hATTR-PN, enabling timely intervention25

  • List of characteristics for each neuropathy is not all-inclusive.
  • *Presence and severity of specific symptoms may depend on the duration and control of diabetes.8
  • †CIDP may present with various phenotypes. This chart describes characteristics of typical CIDP.9,13
  • ‡Symptoms of motor involvement typically become more prominent as hATTR-PN progresses.7
  • §GI manifestations, such as chronic diarrhea and constipation, are often considered autonomic symptoms.3,7
  • ||Over 50% of patients develop CTS before diagnosis.17,23
  • Polyneuropathy due to ATTR can be 10 times more rapid than diabetic neuropathy.26

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FOOTNOTES AND ABBREVIATIONS

Afib, atrial fibrillation; AL-CM, light-chain cardiac amyloidosis; ATTR, transthyretin-mediated amyloidosis; ATTR-CM, cardiomyopathy of transthyretin-mediated amyloidosis; ATTRwt, wild-type transthyretin-mediated amyloidosis; CIDP, chronic inflammatory demyelinating polyneuropathy; CM, cardiomyopathy; CTS, carpal tunnel syndrome; EMG, electromyography; GI, gastrointestinal; hATTR, hereditary transthyretin-mediated amyloidosis; hATTR-PN, polyneuropathy of hereditary transthyretin-mediated amyloidosis; HFpEF, heart failure with preserved ejection fraction; NCS, nerve conduction study; PN, polyneuropathy; sFLC, serum free light chain; SIFE, serum immunofixation electrophoresis; SNAP, sensory nerve action potential; TTR, transthyretin; UIFE, urine immunofixation electrophoresis.

REFERENCES

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