A case of familial amyloid polyneuropathy (FAP ATTR Ile107Val) with proximal muscle weakness in the lower extremities

Abstract

Proximal dominant muscle weakness is rare in transthyretin (TTR)related familial amyloid polyneuropathy (FAP). A 69yearold Japanese man developed numbness and dysesthesia of the first, second and third digits of both hands since 2008. He presented to our hospital with one year history of progressive proximal muscle weakness in the lower extremities since 2013. Neurological examinations revealed predominant proximal muscle weakness and atrophy with areflexia in the lower extremities, decreased superficial sensation in the first, second and third fingers of both hands, and decreased superficial and deep sensation in the lower extremities. Nerve conduction studies revealed an axonal degeneration type of sensorimotor polyneuropathy and bilateral carpal tunnel syndrome. Electromyogram revealed acute and chronic neurogenic changes predominantly in proximal muscles. We performed biopsy of the left quadriceps muscle and observed neurogenic changes in the muscle tissue and an amyloid deposition in the adipose tissue. This amyloid deposition was not seen in endomysium, perimysium and blood vessels. Genetic analysis of the TTR gene revealed the patient was heterozygous for a single nucleotide substitution c.379 A>G, which resulted in the replacement of valine with isoleucine at position 107 of the mature protein. We diagnosed his condition as FAP with Amyloid Transthyretin (ATTR) Ile107Val.

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features

“…ATTRIle107Val was considered as a mixed-phenotype mutation in a review in 2013 [6], but ATTRHis88Arg was recognized only in 2019 as a pathogenic mutation in ATTRv guidelines [25]. ATTRIle107Val was reported in many countries: for example, in Japan [26,27], France [28][29][30], Brazil [31], and Germany [32], although in a recent review of ATTRv, only 11 individuals were identified with ATTRIle107Val in Western Europe [33]. Data showed that the phenotype associated with ATTRIle107Val ATTRv is mixed: cardiac and neurologic features are both present, although the heart is predominantly involved [6,25].…”