[The diagnosis and management of familial amyloid polyneuropathy].

INTRODUCTION: Familial amyloid polyneuropathy designates a group of dominantly inherited neuropathies, with extracellular deposition of amyloid substance in various tissues.

BACKGROUND: The 3 main precursor proteins encountered in these disorders are transthyretin, apolipoprotein A1 or gelsolin. Among them, transthyretin neuropathies are by far the most frequent type with a severe sensori-motor and autonomic neuropathy as the hallmark of the disease, most often associated with cardiac manifestations. First described in Portugal, the affection was subsequently reported across the world, although Portugal, Japan and Sweden are the 3 main areas of prevalence. In the past years, an increasing number of mutations have been identified in the TTR gene, along with a larger clinical spectrum than initially thought. Variable age of onset and penetrance are also largely reported with unclear phenotypic-genotypic correlations. Indeed, the contribution of the molecular genetics is important to ensure the diagnosis at an early stage, but also for predictive diagnosis, in the setting of genetic counselling.

PERSPECTIVES: Over the last 15 years, liver transplantation (LT) has enabled improved prognosis of this devastating condition.

FUTURE PROSPECTS: at present, such procedure should be performed in Val30Met patients, as early as possible in the course of the disease. Experience with such procedure in patients with other TTR variants remains scarce. Other therapeutic strategies are awaited.

CONCLUSION: This review summarizes the recent data on the diagnosis and management of patients and families affected with TTR amyloid neuropathy.