title: Transthyretin-related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset.
abstract: Transthyretin-related familial amyloidotic polyneuropathy (TTR-FAP) usually presents itself as a progressive sensorimotor polyneuropathy with severe autonomic dysfunction and cardiomyopathy. Eighteen patients carrying the Leu64 mutation underwent a series of regular follow-ups, including: neurological examination, electroneurography, electromyography, electrocardiography and echocardiography, blood analysis, a questionnaire on autonomic symptoms, cardiovascular autonomic tests and a 99mTc-DPD examination study. A late onset of a slowly progressive disease which reached its terminal stage after about 10  years was observed. The onset was mainly a length-dependent sensory neuropathy, although a focal onset with carpal tunnel syndrome was detected in three patients. At the onset of the disease, autonomic dysfunction was present in a small number of patients, but, within a few years, this had manifested in all members of the sample group. The only extra-neurological manifestations were cardiac related. It is reasonable to consider Southern Italy as an endemic focus of TTR-FAP. An underestimation of disease prevalence could be caused by a late onset of FAP, which can manifest in patients up to their late 70s. Follow-up of asymptomatic individuals may permit the early detection of symptoms and signs, allowing a detailed record of the natural history of the disease from the beginning and facilitating prompt treatment.
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy. massimorusso81@hotmail.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Russo
authors.forename: Anna
authors.initials: A
authors.lastname: Mazzeo
authors.forename: Claudia
authors.initials: C
authors.lastname: Stancanelli
authors.forename: Rita
authors.initials: R
authors.lastname: Di Leo
authors.forename: Luca
authors.initials: L
authors.lastname: Gentile
authors.forename: Gianluca
authors.initials: G
authors.lastname: Di Bella
authors.forename: Fabio
authors.initials: F
authors.lastname: Minutoli
authors.forename: Sergio
authors.initials: S
authors.lastname: Baldari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vita
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D001706:Biopsy; D015331:Cohort Studies; D004164:Diphosphonates; D018450:Disease Progression; D004576:Electromyography; D005260:Female; D005500:Follow-Up Studies; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology; D009154:Mutation / Q000235:genetics; D009460:Neurologic Examination; D015609:Organotechnetium Compounds; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics* / Q000502:physiology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals
chemical_list: D004164:Diphosphonates; D015609:Organotechnetium Compounds; D011228:Prealbumin; D019275:Radiopharmaceuticals; C033905:technetium Tc 99m 1,1-diphosphonopropane-2,3-dicarboxylic acid; D007930:Leucine