Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid deposits in leptomeningeal vessels, subarachnoid, subpial, and subependymal cerebrospinal regions, spinal ganglia, peripheral nerves, and some internal organs (predominantly heart and kidney) characterize a dominantly inherited disease in a Hungarian family. We found four definitely and three probably affected members in this family of 56 persons in four generations. Clinical features in all definitely diseased patients include disturbance of memory, psychomotor deceleration, ataxia, and hearing loss. In most patients there was temporary disorientation, migraine-like headache with vomiting, and tremor. Some patients had nystagmus, pyramidal signs with spastic paraparesis, hallucinations, urinary retention, and obstipation. Single patients had facial tics 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 along the sylvian fissure; MRI after contrast administration showed prominent enhancement at the surface of the sylvian fissures, brainstem, and cerebellum. Autopsy data was available in three definitely affected patients and in one unaffected family member. Immunohistochemistry identified the amyloid deposits as of the AF (transthyretin, TTR) type; DNA studies revealed a novel TTR missense mutation at codon 18 (TTR Asp18Gly). According to clinical features, pathologic alterations, and molecular studies, this disease is a novel type of systemic familial amyloidosis with disease manifestation clinically restricted to the CNS. It is similar to the oculoleptomeningeal amyloidoses but can be clinically diagnosed by characteristic CTs and the absence of progressive visual impairment.
 ...
PMID:Familial meningocerebrovascular amyloidosis, Hungarian type, with mutant transthyretin (TTR Asp18Gly) 896 Jul 46

Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear.
 ...
PMID:Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient. 2548 73