FAP

FAP is an acronym for familial amyloid polyneuropathy, a hereditary form of systemic amyloidosis caused by mutations in the transthyretin (TTR) gene. Mutant transthyretin misfolds and forms amyloid deposits that accumulate in nerves and various organs, including the peripheral nervous system, heart, eyes, kidneys, and gastrointestinal tract.

The condition is typically inherited in an autosomal dominant pattern with variable penetrance. The most studied mutation is Val30Met, but many other TTR variants exist with differing geographic clustering. Endemic regions have historically higher prevalence, including parts of Portugal, Sweden, Japan, and Brazil, although cases occur worldwide. Onset usually occurs in adulthood and disease progression is gradual.

Clinically, FAP most often presents as a length-dependent sensorimotor neuropathy with autonomic dysfunction. Patients may experience numbness, tingling, burning pain in the feet and hands, orthostatic hypotension, gastrointestinal symptoms, and urinary issues. Cardiac involvement can include restrictive cardiomyopathy and arrhythmias; ocular amyloidosis may cause vitreous opacities and other eye problems. The disease burden varies by mutation and organ involvement, contributing to a heterogeneous presentation.

Diagnosis relies on clinical suspicion supported by genetic testing for TTR mutations and confirmation of amyloid deposits via tissue biopsy with Congo red staining and typing methods. Cardiac imaging and nerve conduction studies aid assessment of organ involvement.

Treatment aims to reduce mutant TTR production or stabilize the protein. Liver transplantation was used historically. Pharmacologic TTR stabilizers (tafamidis, diflunisal) and gene-silencing therapies (patisiran, inotersen, and newer RNAi agents such as vutrisiran) can slow progression. Supportive care for neuropathy and autonomic symptoms remains essential. The prognosis varies with mutation, organ involvement, and access to disease-modifying therapies.

The acronym FAP can denote other terms in different fields, but this article focuses on familial amyloid polyneuropathy.