Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial amyloid polyneuropathy (FAP) is clinically characterized by polyneuropathy and autonomic failure but it shows diverse clinical pictures in different families. We presented clinical and molecular biological findings for a peculiar family in which type I FAP and spinocerebellar ataxia type 1 (SCA-1) coexist. Type IV FAP which is also called familial amyloidosis, Finnish type (FAF), shows the triad of corneal lattice dystrophy, cranial neuropathy and various skin changes. Recently, 3 FAF families were reported in our country, and their clinical pictures and gene abnormalities closely resembled those seen in Finnish patients with this disease. FAP had long been considered to be a genetically determined incurable disorder. Since it has been shown that the precursors of amyloid fibrils (variant forms of transthyretin) in this disorder are produced mainly in the liver, successful results of liver transplantation (LT) were reported in several countries. In our country there are many FAP patients, but LT from a cadaveric donor is still not possible. We, therefore, performed a partial LT for 3 FAP patients using a graft taken from healthy family members, resulting in good outcomes. It seems likely that this partial LT is a very promising therapeutic approach for FAP patients.
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PMID:[Variable clinical manifestations of familial amyloid polyneuropathy and living related liver transplantation]. 875 21

Gelsolin-related amyloidosis (familial amyloidosis, Finnish type) is a rare disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene mutation. Facial palsy, mild peripheral neuropathy, and corneal lattice dystrophy are characteristic, but atrophic bulbar palsy, ataxia of gait, and minor cognitive impairment may occur. In histological and immunohistochemical studies of the central nervous system in 4 patients with a G654A gelsolin mutation, we found widespread spinal, cerebral, and meningeal amyloid angiopathy, with deposition of gelsolin-related amyloid (AGel). Marked extravascular deposits occurred in the dura, spinal nerve roots, and sensory ganglia. The amyloid deposits were also variably immunoreactive for apolipoprotein E (ApoE), alpha1-antichymotrypsin (alpha1-ACT), and cystatin C (Cys C). Cerebral perivascular fibrinogen immunoreactivity was occasionally noted. The patients showed posterior column degeneration and diffuse loss of myelin in the centrum semiovale with perivascular accentuation. Postmortem magnetic resonance imaging, performed on 1 patient, showed white matter lesions, colocalizing with the histological abnormalities. Our study shows that deposition of AGel in the spinal and cerebral blood vessel walls, meninges, as well as spinal nerve roots and sensory ganglia is an essential feature of this form of systemic amyloidosis and may contribute to the central nervous system symptoms.
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PMID:Gelsolin-related spinal and cerebral amyloid angiopathy. 1007 44

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78-year-old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 years he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin-actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.
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PMID:Severe ataxia with neuropathy in hereditary gelsolin amyloidosis: a case report. 1745 28

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78- year old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin - actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.
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PMID:Severe ataxia with neuropathy in hereditary gelsolin amyloidosis. 1984 87