[Familial amyloidotic polyneuropathy (FAP type I) with late-onset; siblings showing heterogeneity in age of onset]

Abstract

A 66-year-old man with late-onset FAP type I with Val30-->Met mutation in transthyretin was described. The age of clinical onset was 62 years old. The somatic motor and sensory involvement predominantly distributing in the distal part of the extremities preceded the manifestation of autonomic symptoms. He was diagnosed as having somatic motor and sensory neuropathy. However, 4 years after the onset, autonomic symptoms such as orthostatic hypotension, alternating constipation and diarrhea developed. Sural nerve biopsy and DNA study established the diagnosis of FAP type I. A 77-year-old brother of this patient, also had the type I mutation of transthyretin, but did not show any neurological symptoms or electrophysiological abnormalities, indicating significant discordance to the onset age of clinical phenotypes in this family. As suggested in an experiment on transgenic mice with FAP gene, factors other than FAP gene, possibly an environmental factor, may have been related with the clinical onset of FAP. Both siblings in this family, had FAP type I gene mutations, yet showed a significant discordance to the phenotypic manifestations of FAP. This supports the view that multifactorial background may well influence the clinical onset and progression of this disease.