TRANSTHYRETIN AMYLOIDOSIS - A NEW MUTATION ASSOCIATED WITH DEMENTIA

Familial transthyretin (TTR) amyloidosis commonly presents with periph eral neuropathy and involvement of visceral organs. In contrast, signs of central nervous system (CNS) involvement are exceptional. We repor t that members of a kindred affected by a slowly progressive dementia, seizures, ataxia, hemiparesis, and decreased vision without neuropath y have TTR amyloid deposits in the leptomeninges, the brain parenchyma , and the eye. This condition, previously labeled oculoleptomeningeal amyloidosis, is linked to a mutation at codon 30 of TTR gene, resultin g in the substitution of valine with glycine in this family, TTR amylo id deposits were present in the leptomeninges, especially the leptomen ingeal vessels, and in the subependymal regions of the ventricular sys tem where they disrupted the ependymal lining and resulted in amyloid- glial formations protruding into and narrowing the ventricular system. Hydrocephalus and atrophy and infarction of cerebral and cerebellar c ortexes were also present. Review of the literature shows that amyloid deposition in the leptomeninges is not uncommon in TTR amyloidoses cl inically characterized by peripheral neuropathy and lack of CNS signs. The present kindred, which presented exclusively with signs of CNS in volvement, expands the phenotype of TTR amyloidosis and raises questio ns concerning the mechanisms determining phenotypic expression in TTR familial amyloidosis.