Neurológia pre prax 6/2013

Familial amyloid polyneuropathy

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a severe hereditary neuropathy due to deposition of mutant protein transtyretin (TTR) as amyloid. TTR-FAP is primarily characterized by sensory, motor and autonomic neuropathy and/or cardiomyopathy. As TTR-FAP is a progressive, disabling and life-threatening polyneuropathy, it is important to secure an accurate diagnosis as soon as possible. It is important to suspect de novo TTR-FAP among patients with idiopathic progressive peripheral neuropathies. Especially in elderly TTR-FAP should be considered as a chameleon-like-neuropathy mimicking a large spectrum of peripheral neuropathies. Laboratory tests (e.g. salivatory gland biopsy, nerve biopsy) are specific to identify amyloid deposits, but not enough sensitive. TTR gene sequencing is the most sensitive diagnostic method. 113 mutations in the TTR gene are known to promote the amyloid process. TTR Val30Met is the most frequent mutation (> 60 %), the Slovak patients have a rare mutation Val71Ala. If untreated the disease has an inexorable progressive course and death occurs 10 years of symptoms onset. Because the mutant form of TTR is produced mainly in the liver, orthotopic liver transplantation was initiated in 1990 in order to halt the progression of the disease. Liver transplantation was, until recently, the only available treatment but is associated with significant morbidity and mortality. Tafamidis is the first drug that selectively binds to transthyretin preventing its dissociation into amyloid. Tafamidis was shown to delay disease progression and was well tolerated. In november 2011 was tafamidis approved in Europe to treat neuropathy in stage 1 TTR-FAP patients.

Keywords: familial amyloid polyneuropathy, transthyretin, TTR gene mutations, de novo TTR-FAP, DNA diagnosis, liver transplantation, tafamidis.