Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis

Brain. 1999 Feb:122 ( Pt 2):183-90. doi: 10.1093/brain/122.2.183.

Abstract

We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR. Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and periods of decreased consciousness. MRI showed a marked enhancement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy. The simultaneous presence of extensive visceral amyloid and clinically significant deposits affecting both the peripheral and central nervous system extends the spectrum of amyloid-related disease associated with TTR mutations. The unusual association of severe peripheral neuropathy with symptoms of leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amyloid Neuropathies / diagnostic imaging
  • Amyloid Neuropathies / genetics*
  • Amyloid Neuropathies / pathology
  • Ependyma / blood supply
  • Ependyma / pathology
  • Exons / genetics
  • Female
  • Gadolinium
  • Genetic Variation
  • Humans
  • Iodine Radioisotopes
  • Kidney / diagnostic imaging
  • Leucine
  • Liver / diagnostic imaging
  • Magnetic Resonance Imaging
  • Meninges / blood supply
  • Meninges / pathology
  • Phenotype
  • Point Mutation*
  • Polymorphism, Genetic
  • Prealbumin / genetics*
  • Proline
  • Radionuclide Imaging
  • Sequence Analysis, DNA
  • Serum Amyloid P-Component / metabolism
  • Serum Amyloid P-Component / pharmacokinetics
  • Spleen / diagnostic imaging

Substances

  • Iodine Radioisotopes
  • Prealbumin
  • Serum Amyloid P-Component
  • Proline
  • Gadolinium
  • Leucine