P.185 - Pathologically and genetically diagnosed familial amyloid polyneuropathy

Abstract

Familial amyloid polyneuropathy (FAP) is an autosomal dominantly inherited disorder, in which transthyretin (TTR) is the most frequent causative gene. TTR-related FAP has been mainly reported in Portugal, Japan, Sweden, and only a few families have been diagnosed in Korea so far. Herein, we report another family with FAP in Korea. A 47-year-old man presented with 3-year history of numbness in distal extremities and orthostatic dizziness. Progressive leg weakness developed 2 years prior to the visit, which was followed by constipation, dry mouth, and dry eyes. His mother had been diagnosed as cardiac amyloidosis and died in her 60s. On examination, muscle atrophy and weakness were evident in both legs, accompanied by bilateral foot drop. Pain sensation was decreased diffusely in upper and lower limbs, and vibration and proprioception were impaired below ankles with positive Romberg sign. Deep tendon reflex was absent in all extremities. He had unequal sized pupils which did not respond to the light. Laboratory tests were unremarkable. Nerve conduction study (NCS) was compatible with diffuse sensorimotor polyneuropathy. Autonomic function test (AFT) represented severe pan-autonomic dysfunction. Transthoracic echocardiography showed a concentric left ventricular hypertrophy with normal left ventricular contractility. Sural nerve biopsy confirmed deposit of amyloid with loss of myelinated nerve fibers. PCR-Sanger sequencing revealed a heterozygous mutation in TTR (p.A56P), which had been reported pathogenic in FAP families. The same mutation was detected in his sister who did not complain any sensorimotor symptoms but occasional orthostatic dizziness; neither NCS nor AFT could detect any abnormality. High awareness is required to diagnose these paucisymptomatic cases before irreversible amyloid accumulation take place.