Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neville and coauthors (1973) reported several cases of neurovisceral storage disease with vertical supranuclear gaze paresis, ataxia and other central nervous disorders. This disease is classified into Niemann-Pick disease type C because of the presence of foamy cells or sea-blue histiocytes in bone marrow, and the accumulation of sphingomyelin, cholesterol and other glycosphingolipids. In this paper, we reported a rare case of neurovisceral storage disease with severe horizontal supranuclear ophthalmoplegia and sea-blue histiocyte in bone marrow. The patient was a 9-year-old boy. He was hospitalized for unstable gait. The neurological examination revealed severe horizontal supranuclear ophthalmoplegia, moderate ataxia of four extremities and trunk, and mild dystonia of neck and four limbs on walking and standing. The ocular movement in the vertical direction was less impaired and his mentality was almost normal. The bone marrow aspiration showed a few sea-blue histiocytes. The activities of fibroblast lysosomal enzymes including sphingomyelinase were normal. The rectal biopsy revealed many foamy cells in mucous membrane and submucosa. The cell had PAS-positive and acid phosphatase-positive substances, which showed rose-red metachromasia with Feyrter's thionin method. But these abnormal cells were never stained by Sudan black B. These histochemical reactions were compatible with those of Neville's neurovisceral storage disease (Lake, 1983). Therefore we supposed the pathogenesis of this case was the same as that of Neville's cases. In this case, the horizontal supranuclear ophthalmoplegia was a unique symptom.
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PMID:[A case of neurovisceral storage disease with sea-blue histiocyte and severe horizontal supranuclear ophthalmoplegia]. 233 23

This paper examines the topography of neuronal degeneration in the central nervous system of the dystonia musculorum (dt) mutant mouse, revealed by selective silver impregnation, specific histochemical staining and electron microscopy. Neuronal lesions have been observed exclusively in the spinal cord, the medulla and the anterior lobe of the vermis. In the spinal cord, axonal degeneration was maximal among large and medium-sized primary sensory fibers, whereas thin caliber primary afferents were unaffected, with the exception of those containing acid phosphatase activity. In regions of laminae VI to VIII that receive numerous degenerative primary afferents, neurons undergoing different phases of degeneration (chromatolysis, lipid accumulation, dark shrunken necrosis) were constantly found. Most of the latter belonged to spinocerebellar neurons, owing to the presence of fiber degeneration in both spinocerebellar tracts and mossy fiber degeneration in the anterior vermal lobe. In the medulla only axonal degeneration was observed and was confined to three fiber systems: the dorsal column pathway, the sensory trigeminal fibers (both from the trigeminal ganglion and from the mesencephalic trigeminal nucleus), and the spinocerebellar fibers entering the cerebellum through the inferior and superior cerebellar peduncles. This study also suggests a simple pathophysiological mechanism for the onset and the progression of the degeneration: dystonic gene action would affect perinatally specific classes of sensory receptors, producing the degeneration of the nerve terminals and, progressively, the cell death of the sensory ganglion cells at their origin. This retrograde death, which results in the massive and early deafferentation of spinocerebellar neurons, would provoke, trans-neuronally, the impairment of these second order sensory neurons and the progressive degeneration of the spinocerebellar system. The close resemblance of the neuropathology of the mutant mouse to Friedreich's ataxia (the commonest form of human degenerative ataxic disorders) allows one to suppose that the dystonic mouse may be an optimal animal model for studying the genetic basis and the pathophysiological mechanisms of this form of human ataxia.
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PMID:Pathologic changes in the CNS of dystonia musculorum mutant mouse: an animal model for human spinocerebellar ataxia. 321

TOR1A/TorsinA mutations cause two incurable diseases: a recessive congenital syndrome that can be lethal, and a dominantly-inherited childhood-onset dystonia (DYT-TOR1A). TorsinA has been linked to phosphatidic acid lipid metabolism in Drosophila melanogaster. Here we evaluate the role of phosphatidic acid phosphatase (PAP) enzymes in TOR1A diseases using induced pluripotent stem cell-derived neurons from patients, and mouse models of recessive Tor1a disease. We find that Lipin PAP enzyme activity is abnormally elevated in human DYT-TOR1A dystonia patient cells and in the brains of four different Tor1a mouse models. Its severity also correlated with the dosage of Tor1a/TOR1A mutation. We assessed the role of excess Lipin activity in the neurological dysfunction of Tor1a disease mouse models by interbreeding these with Lpin1 knock-out mice. Genetic reduction of Lpin1 improved the survival of recessive Tor1a disease-model mice, alongside suppressing neurodegeneration, motor dysfunction, and nuclear membrane pathology. These data establish that TOR1A disease mutations cause abnormal phosphatidic acid metabolism, and suggest that approaches that suppress Lipin PAP enzyme activity could be therapeutically useful for TOR1A diseases.
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PMID:Excess Lipin enzyme activity contributes to TOR1A recessive disease and DYT-TOR1A dystonia. 3251 4