Transthyretin amyloidosis: diagnosis and treatment
Hereditary transthyretin amyloid (ATTR) amyloidosis is a rare, fatal disease. Over 100 amyloidogenic TTR point mutations have been described, 15 of which are found in the Swedish population. The most common TTR mutation in Sweden is the TTRV30M mutation (c.148G>A, p.Val50Met) characterised by an exchange of the amino acid methionine for valine at position 30 of the mature protein. TTR mutations are mostly associated with serious heart and neurological complications, whereas cardiac complications alone dominate the clinical presentation in senile systemic amyloidosis (SSA) which is caused by wild-type TTR and affects around 20% of all men over 80 years of age.
Even though the onset of the disease generally is above the age of 50, early onset from 30 years of age is not uncommon. The patients typically present with an axonal peripheral polyneuropathy that affects the somatic and autonomic nervous systems leading to loss of sensation and motor function and pronounced neuropathic pain.Severe gastrointestinal, kidney and bladder dysfunction develop with time, and at the end stage of the disease, the patients are severely malnourished, incapacitated, bedridden or bound to a wheel chair, with urinary and faecal incontinence. In addition, heart complications in the form of arrhythmia and/or cardiomyopathy are common and may proceed the development of polyneuropathy or be the only symptom of the disease. Untreated, the disease is fatal with an expected survival for Swedish patients of approximately 13 years, though variations are encountered with individual patients surviving up until 20 years.
The aim of our research is to improve diagnostic and prognostic methods as well as to explore different treatment methods that hopefully will lead to effective treatment for this fatal disease.