Objective: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation.
Background: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described.
Methods: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient.
Results: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member.
Conclusions: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.