Familial amyloid polyneuropathy is an inherited systemic peripheral polyneuropathy affecting the sensomotoric and autonomic nervous systems. The disease usually occurs in the third to fifth decade of the patient’s life. It is endemic, and especially common in people from Portugal and Japan.
The disease is inherited autosomal dominant. Mutations in the TTR gene at the locus 18q12.1 are causative. TTR, formerly known as prealbumin, encodes the transesteritrogen, transthyretin, which is mainly secreted by the liver.
The genetic changes cause the abnormal folding of this protein and the deposition of misfolded fibrillar proteins as amyloids. Typically, there is an initial sensory slow progressive neuropathy with loss of pain and temperature perception, paresthesia and trophic lesions of the feet.
In the course of the motor neuropathy occurs. In some patients, especially those with early onset disease, autonomic neuropathy is the first manifestation of the disease. Findings may include: postural hypotension, gastrointestinal symptoms, sexual dysfunction, anhidrosis, urinary retention or incontinence.
Depending on the type of mutation, in addition to polyneuropathy, cardiac symptoms also occur, usually in the form of progressive cardiomyopathy. Patients with leptomeningeal amyloidosis may suffer from CNS findings including: dementia, psychosis, seizures, motor paresis, ataxia or intracranial haemorrhage.
Since the liver is the major organ of the synthesis of amyloidogenic transthyretin, orthotopic liver transplantation is the only promising therapeutic option.