FAMILIAL MENINGOCEREBROVASCULAR AMYLOIDOSIS, HUNGARIAN TYPE, WITH MUTANT TRANSTHYRETIN (TTR ASP18GLY)

Amyloid deposits in leptomeningeal vessels, subarachnoid, subpial, and subependymal cerebrospinal regions, spinal ganglia, peripheral nerves , and some internal organs (predominantly heart and kidney) characteri ze a dominantly inherited disease in a Hungarian family. We found four definitely and three probably affected members in this family of 56 p ersons in four generations. Clinical features in all definitely diseas ed patients include disturbance of memory, psychomotor deceleration, a taxia, and hearing loss. In most patients there was temporary disorien tation, migraine-like headache with vomiting, and tremor. Some patient s had nystagmus, pyramidal signs with spastic paraparesis, hallucinati ons, urinary retention, and obstipation. Single patients had facial ti es and sleep disorders. Progressive visual disturbance and clinically manifest polyneuropathy were absent. CSF protein was markedly elevated in all patients. CT showed characteristic symmetric calcification alo ng the sylvian fissure; MRI after contrast administration showed promi nent enhancement at the surface of the sylvian fissures, brainstem, an d cerebellum. Autopsy data was available in three definitely affected patients and in one unaffected family member. Immunohistochemistry ide ntified the amyloid deposits as of the AF (transthyretin, TTR) type; D NA studies revealed a novel TTR missense mutation at codon 18 (TTR Asp 18Gly). According to clinical features, pathologic alterations, and mo lecular studies, this disease is a novel type of systemic familial amy loidosis with disease manifestation clinically restricted to the CNS. It is similar to the oculoleptomeningeal amyloidoses but can be clinic ally diagnosed by characteristic CTs and the absence of progressive vi sual impairment.