A Val30Met sporadic familial amyloid polyneuropathy case with atypical presentation: upper limb onset of symptoms

Excerpt

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by the mutations of the transthyretin (TTR) gene. The mutant amyloidogenic TTR protein causes systemic accumulation of amyloid fibrils that result in organ dysfunction [1]. Over 100 mutations in TTR gene are associated with the disease but still, the first identified Val30Met mutation make up 50% of the cases worldwide. In the three main regions in which TTR-FAP is endemic (Portugal, Sweden and Japan), the Val30Met mutation is the predominant genetic cause. However, in non-endemic regions genetic features are more heterogeneous [2]. Clinical presentation is highly variable due to the interplay between several factors consisting of genotype, geographical origin of the patient, regional variation, penetrance of gene mutation and age at onset of symptoms [2]. Length-dependent axonal sensory–motor and autonomic polyneuropathy is the hallmark feature of TTR-FAP hence, lower limb sensory symptoms are generally the initial manifestations. Yet, Koike et al. reported that 5 of 50 patients presented with upper limb sensory symptoms [3]. Herein, we describe a patient with Val30Met mutation presented with asymmetrical upper limb symptoms which was not previously reported in non-endemic regions. …