Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An unusual neurovisceral lipid storage disorder in two unrelated juvenile patients manifested itself by dystonia and involuntary movements, with facial grimacing, dysarthria, gait difficulty, and impaired manual dexterity. Supranuclear paresis of vertical gaze and splenomegaly were present. Absent were seizures, major intellectual deterioration, spasticity, or blindness. Histiocytes showed lysosomal storage of various phospholipids, cholesterol, neutral lipids, and autofluorescent material. Appendiceal neurons showed only an increse of phospholipids by histochemistry. Neuronal deposits differed ultrastructurally from these in histiocytes. Leukocyte sphingomyelinase activity was normal. The nosology of this disease and its relationship to so-called juvenile types of Niemann-Pick disease is discussed. The primary metabolic defect in these patients remains unknown.
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PMID:Juvenile dystonic lipidosis: an unusual form of neurovisceral storage disease. 18 51

Sphingolipidoses are an heterogeneous group of inherited disorders of lipid metabolism affecting primarily the central nervous system. These disorders occur chiefly in the pediatric population, and the degenerative nature of the disease processes is generally characterized by diffuse and progressive involvement of neurones (gray matter) with psychomotor retardation and myoclonus or of fiber tracts (white matter) with weakness and spasticity. Biochemical research has identified the defects in the sphingolipidoses to specific lysosomal enzymes. For example, Niemann-Pick disease lacks sphingomyelinase; Krabbe's disease lacks galactocerebrosidase; Gaucher's disease lacks beta-D-glucosidase; metachromatic leukodystrophy lacks sulfatase; Tay-Sachs disease lacks hexosaminidase A; and generalized gangliosidosis lacks beta-galactosidase. Although there are no currently available modes of rendering corrective therapy in these disorders, a definitive diagnosis is possible both antepartum as well as postpartum. This information provides a sound and accurate basis for genetic counseling.
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PMID:Sphingolipidoses. 555 2

Niemann Pick disease type C (NPC) is a neurovisceral disorder due to mutations in NPC1 or NPC2. This review focuses on poorly characterized clinical and molecular features of early infantile form of NPC (EIF) and identified 89 cases caused by NPC1 (NPC1) and 16 by NPC2 (NPC2) mutations. Extra-neuronal features were common; visceromegaly reported in 80/89 NPC1 and in 15/16 NPC2, prolonged jaundice in 30/89 NPC1 and 7/16 NPC2. Early lung involvement was present in 12/16 NPC2 cases. Median age of neurological onset was 12 (0-24) and 7.5 (0-24) months in NPC1 and NPC2 groups, respectively. Developmental delay and hypotonia were the commonest first detected neurological symptoms reported in 39/89 and 18/89 NPC1, and in 8/16 and 10/16 NPC2, respectively. Additional neurological symptoms included vertical supranuclear gaze palsy, dysarthria, cataplexy, dysphagia, seizures, dystonia, and spasticity. The following mutations in homozygous state conferred EIF: deletion of exon 1+promoter, c.3578_3591 + 9del, c.385delT, p.C63fsX75, IVS21-2delATGC, c. 2740T>A (p.C914S), c.3584G>T (p.G1195V), c.3478-6T>A, c.960_961dup (p.A321Gfs*16) in NPC1 and c.434T>A (p.V145E), c.199T>C (p.S67P), c.133C>T (p.Q45X), c.141C>A (p.C47X) in NPC2. This comprehensive analysis of the EIF type of NPC will benefit clinical patient management, genetic counselling, and assist design of novel therapy trials.
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PMID:Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease. 3270 31