Clinical, neuropathological and genetic findings in patients with transthyretin-associated familial amyloid polyneuropathy

Objective To investigate the clinical, electrophysiological, histopathological and genetic findings in patients with transthyretin (TTR) -associated familial amyloid polyneuropathy (FAP) (TTR-FAP) in China. Methods Familial or sporadic cases of TTR-FAP of Chinese Han orgin diagnosed at Peking Union Medical College Hospital in the past eight years (2006-2014) were retrospectively reviewed. Clinical, neuropathological and genetic characteristics of these patients were evaluated. Results Thirteen cases with TTR-FAP diagnosed by pathology and genetic screening were collected. Clinically, all patients exhibited distal symmetric motor and sensory neuropathy with sensory loss of the lower and upper limbs. Five patients experienced muscle pain, 2 had transient ischemic attack and all had various autonomic involvements. Other affected organs include cardiomyopathy in 12 cases, thyroid infiltration in 3 cases and leptomeningeal enhancement in 4. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Histologically, 5 of 10 patients were found amyloid deposit in peripheral nerve. All the cases were positive for muscular amyloid and TTR immuonstaining. TTR-positive amyloid deposits were detected in 5 of 11 patients who performed peripheral nerve biopsy and in all the 10 cases that performed muscle TTR staining. Genetically, of the 13 TTR-FAP patients, 9 reported and one novel TTR mutations (E54Q) were identified in the TTR gene. Conclusions TTR-FAP may be under-diagnosed in Chinese population and should be considered in patients with chronic progressive neuropathy accompanied by multisystem involvements. Combined biopsy of peroneus brevis muscle and superficial peroneal nerve might be a prime choice to get positive pathological findings. Genetic screening is mandatory but no specific genotype-phenotype correlations should be expected. G47R may be the most common mutation in Chinese FAP cases. Key words: Amyloid neuropathies, familial; Prealbumin; Mutation; Biopsy