Neurológia pre prax 4/2019
Sporadic form of late-onset transthyretin familial amyloid polyneuropathy – first case report in Slovak Republic
Transthyretin familial amyloid polyneuropathy (TTR FAP) is a severe and rare hereditary neuropathy with autosomal dominant inheritance with pathogenic mutations in TTR gene. TTR FAP is caused by an abnormal protein transthyretin (TTR) produced by liver. Pathogenic amyloidogenic mutations are responsible for destabilisation of TTR tetramere and monomere association into amyloidogenic formations. Amyloid is placed in all peripheral nerves, causing their destruction. TTR FAP is primarily characterized by progressive sensory, motor and autonomic neuropathy. In advanced stages there are severe neurological symptoms – flaccid paralysis, global muscle atrophy, severe sensitivity disturbances for all qualities and severe symptoms of autonomic organ dysfunctions. TTR FAP is a progressive, disabling and life-threatening polyneuropathy. If untreated the disease has an inexorable progressive course and death occurs within 10 years of symptoms onset. Tafamidis has brought an essential breakthrough in treatment and prognosis of TTR FAP patients. Tafamidis acts as a specific TTR stabilizer, prohibits TTR transformation into amyloid and its deposition to peripheral nerves. The hereditary TTR FAP occurs in two forms: early-onset TTR FAP has an onset in young age (25–35 years); late-onset TTR FAP occurs in elder age over 50–60 years. Sporadic form of transthyretin familial amyloid polyneuropathy is caused by de novo mutations in TTR gene. Sporadic forms are very rare, also undiagnosed, and usually manifesting as idiopathic sporadic progressive axonal polyneuropathy. The definitive diagnosis of all 3 TTR FAP forms is confirmed by DNA evidence of pathogenic mutations in TTR gene. As TTR FAP is a progressive, disabling and life-threatening polyneuropathy, it is important to secure an accurate diagnosis as soon as possible in familial and sporadic TTR FAP forms. It is important to suspect de novo TTR FAP among patients with idiopathic progressive axonal peripheral neuropathies and painful sensitive neuropathies. We describe in our article first case report of sporadic form of late-onset transthyretin familial amyloid polyneuropathy in Slovakia caused by pathogenic mutation Ile127Val in TTR gene.
Keywords: transthyretin familial amyloid polyneuropathy (TTR FAP), pathogenic mutations in TTR gene, transthyretin, early-onset TTR FAP, late-onset TTR FAP, sporadic form of TTR FAP, DNA diagnosis, treatment
