Familial amyloidosis with polyneuropathy type I (Portuguese or Andrade type) is an autosomal dominant form of systemic amyloidosis, which was first described in 1952 by Andrade . This type of amyloidosis is geographically clustered in Portugal , northern Sweden  and Japan , but sporadic cases have been reported in other countries such as Ireland, USA and China. Familial amyloidosis with polyneuropathy (FAP) is caused by mutated transthyretin (TTR), in which valine is replaced by methionine in position 30 . The disease is characterized by a progressive polyneuropathy that affects both the peripheral and the autonomic nervous systems . In Swedish FAP patients, the initial clinical manifestation is a sensory motor polyneuropathy starting in the lower extremities and later affecting the upper ones. Symptoms from the autonomic nervous system include orthostatic hypotension, anhidrosis, sexual impotence, heart dysrhythmia and gastrointestinal disturbances . Initial gastrointestinal symptoms are severe constipation, often accompanied by nausea and vomiting. Gradually, the constipation is relieved by periods of diarrhoea which later become continuous . The cause of death is usually intercurrent infections and malnutrition.
Although the mutation of TTR in Japanese and Swedish FAP patients is identical, they disclose different clinical manifestations of the disease. Whilst the mean age of onset in Swedish patients is the middle fifties, that of Japanese patients is middle thirties . In the majority of Japanese FAP patients, autonomic nerves are impaired before sensory and motor nerves . Most Japanese patients exhibit gastrointestinal symptoms such as diarrhoea, constipation, alternating diarrhoea and constipation, nausea and vomiting during the course of the disease. Amongst these symptoms, diarrhoea is more frequently found early in Japanese than Swedish patients .
The neuroendocrine system in the digestive tract plays an important role in regulating motility, secretion, blood flow and ion transport . Recently a reduction of several endocrine cell types has been found in the duodenum and rectum in Swedish FAP patients [10, 11] and it has been suggested that these abnormalities are a contributing factor in the development of gastrointestinal disturbances. The present study was undertaken to investigate if similar reduction of the endocrine cells is present in the colon of Japanese end stage FAP patients.