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oculoleptomeningeal type amyloidosis (amyloidosis VII)

Pathology: - generalized amyloidosis due to transthyretin amyloid deposition - protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis - includes leptomeningeal amyloidosis - amyloid in the walls of leptomeningeal vessels, in pia mater, arachnoid, & subpial deposits - some patients also develop vitreous amyloid deposition Genetics: - associated with defects in transthyretin Clinical manifestations: - seizures - stroke-like episodes - dementia - psychomotor deterioration - visual impairment with vitreous amyloid deposition Management: - experimental - siRNA in a lipid nanoparticle injected IV diminishes serum transthyretin levels for several weeks [2] - inotersen (Tegsedi) or patisiran - no adverse effects noted

Related

transthyretin; ATTR; prealbumin; TBPA (TTR PALB)

General

amyloidosis genetic disease of the central nervous system genetic disease of the peripheral nervous system

Properties

PROTEIN-PRECURSOR: transthyretin

Database Correlations

OMIM 105210

References

  1. OMIM :accession 105210
  2. Coelho T et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med 2013 Aug 29; 369:819 PMID: 23984729 http://www.nejm.org/doi/full/10.1056/NEJMoa1208760 - Lachmann HJ. A new era in the treatment of amyloidosis? N Engl J Med 2013 Aug 29; 369:866 PMID: 23984734 http://www.nejm.org/doi/full/10.1056/NEJMe1308768
  3. Yasgur BS New Agents Show Promise for Severe and Fatal Genetic Disease. Medscape - Jul 10, 2018. https://www.medscape.com/viewarticle/899112