Transplantation hépatique dans les neuropathies amyloïdes familiales

Abstract

Familial amyloid polyneuropathy (FAP) is the most serious of the hereditary neuropathies in adults and is due to endoneurial amyloid deposits. These sensorimotor and autonomic diseases are very progressive and disabling. A "typical" patient with FAP is 30-years-old, of Portuguese origin, and has insidiously developed pains or sensory loss in the feet and digestive disorders, such as diarrhea, and has lost weight. Clinical examination shows sensory polyneuropathy of the distal small fibers (with sensory loss prevailing over sensations of temperature and pain). Cardiac disorders are frequent. One parent will have died prematurely from this disease. FAP are fatal 10.8 years after the first symptoms, on average. Neuropathy is usually associated with cardiac manifestations, weight loss, and more rarely renal or eye complications. FAP are secondary to a point mutation of the transthyretin (TTR) or prealbumin gene (18q11.2-q12.1), of which there are 40 variants. In France, the variant TTRMet30 is present in half of all cases and one third of FAP patients present with sporadic disease. Liver transplantation has been proposed as a treatment for FAP because the liver is the main source of variant amyloidogenic TTR. Transplantation makes it possible to eliminate 98% of the variant TTR in the serum, doubles median survival for variant TTRMet30 carriers, and halts the progress of the sensorimotor neuropathy over the long term in 62% of cases. No regression or recurrence has been observed. Poor prognostic factors after liver transplantation are a mutation other than the TTRMet30 variant, severe neuropathy, and late onset. Liver transplantation must be proposed to the symptomatic patients as early as possible. It should be performed in a center specialized in FAP. After LT, periodic follow-up in such a center is essential.