Transthyretin-related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset

J Peripher Nerv Syst. 2012 Dec;17(4):385-90. doi: 10.1111/j.1529-8027.2012.00436.x.

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.

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial / diagnostic imaging
  • Amyloid Neuropathies, Familial / genetics*
  • Amyloid Neuropathies, Familial / pathology
  • Autonomic Nervous System Diseases / etiology
  • Autonomic Nervous System Diseases / physiopathology
  • Biopsy
  • Cohort Studies
  • Diphosphonates
  • Disease Progression
  • Electromyography
  • Female
  • Follow-Up Studies
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Humans
  • Leucine / genetics*
  • Male
  • Middle Aged
  • Muscle Weakness / etiology
  • Mutation / genetics
  • Neurologic Examination
  • Organotechnetium Compounds
  • Phenotype
  • Prealbumin / genetics*
  • Prealbumin / physiology
  • Radionuclide Imaging
  • Radiopharmaceuticals

Substances

  • Diphosphonates
  • Organotechnetium Compounds
  • Prealbumin
  • Radiopharmaceuticals
  • technetium Tc 99m 1,1-diphosphonopropane-2,3-dicarboxylic acid
  • Leucine