Transthyretin familial amyloid polyneuropathy ( TTR ‐ FAP ): Parameters for early diagnosis

Background Familial transthyretin amyloidosis is a life‐threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy ( TTR ‐ FAP ) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Methods Twenty‐four patients with TTR ‐ FAP and 48 patients with diabetic polyneuropathy ( dPNP ) were investigated (neurological impairment score NIS ; neurological disability score NDS ) in a cross‐sectional design. Both groups were matched for gender and presence of pain. Quantitative sensory testing ( QST ), sympathetic skin response ( SSR ), heart rate variability ( HRV ), and nerve conduction studies ( NCV ) were performed. Both groups were compared using univariate analysis. In a stepwise discriminant analysis, discriminators between both neuropathies were identified. These discriminators were validated comparing TTR ‐ FAP patients with a cohort of patients with chemotherapy‐induced polyneuropathy ( CIN ) and chronic inflammatory demyelinating neuropathy ( CIDP ). Results TTR ‐ FAP patients scored higher in NDS and NIS and had impaired cold detection ( CDT , p  = .024), cold–warm discrimination ( TSL , p  = .019) and mechanical hyperalgesia ( MPT , p  = .029) at the hands, SSR (upper limb, p  = .022) HRV and ulnar and sural NCS (all p  < .05) were more affected in TTR ‐ FAP . Ulnar nerve sensory NCV , CDT , and the MPT but not the other parameters discriminated TTR ‐ FAP from dPNP (82% of cases), from CIN (86.7%) and from CIDP (68%; only ulnar sNCV ). Conclusion Low ulnar SNCV , impaired cold perception, and mechanical hyperalgesia at the hands seem to characterize TTR ‐ FAP and might help to differentiate from other polyneuropathies.