11/19. Juvenile dystonic lipidosis (variant of Niemann-Pick disease type C).In two siblings affected with dementia, epilepsy and vertical supranuclear ophthalmoplegia, foam cells and sea-blue histiocytes were found in the bone marrow. Electron microscopy of skin and neuromuscular biopsies gave presumptive evidence in favour of a storage disorder. Postmortem examination of both cases revealed an intraneuronal polymorphous lysosomal storage in the central nervous system (in the cortex and in many nuclei e.g. the substantia nigra and the reticular formation of the brain stem). In the visceral organs with the spleen most severely affected, the inclusions had a different ultrastructure, being composed of tightly apposed leaflets. The biochemical study revealed accumulation of sphingomyelin and other lipids in liver and spleen, with normal sphingomyelinase activities, which is consistent with the diagnosis of Niemann-Pick disease type C. In the brain, the most striking abnormalities involved the glycolipids. Sphingomyelinase activities were unchanged in cultivated skin fibroblasts. These data compared with those of reported cases, allowed the following conclusions to be made: (1) although the combination of clinical features appears to be unique, none of them, when considered separately, is pathognomonic for juvenile dystonic lipidosis; (2) diagnosis during life can be suggested by careful examination of nerve bundles and fibroblasts with the electron microscope, although the method of choice appears to be the study of bone marrow; but final assessment of the diagnosis, in the absence of demonstrable enzymic deficiency, requires in most cases a study of the lipid profile in a liver biopsy (or better, spleen tissue whenever available); (3) the intralysosomal storage is different, both morphologically and biochemically, in the central nervous system and in the spleen; (4) juvenile dystonic lipidosis represents a juvenile variant of Niemann-Pick disease type C, pending the discovery of the primary defect responsible for this disorder.- - - - - - - - - - ranking = 1keywords = supranuclear ophthalmoplegia, supranuclear, ophthalmoplegia (Clic here for more details about this article) |
12/19. Deficiency of phospholipase C acting on phosphatidylglycerol in Niemann-Pick disease.We examined the degradation of a labeled phosphatidylglycerol (PG) by fibroblasts from a normal control and a patient with Niemann-Pick (NP) disease. The control homogenate had both phospholipase A and phospholipase C activities toward PG, but NP cells had only phospholipase A. The PG phospholipase C of control fibroblasts was solubilized by sonication and freezing and thawing, was most active at pH 5.0, and was inhibited by Ca2-, detergents, sphingomyelin, and 5' AMP. Assay of PG phospholipase C in fibroblast cultures from NP patients with sphingomyelinase deficiency (three designated type A and four type B) confirmed absence of activity, whereas cultures from NP patients without sphingomyelinase deficiency (three designated type C and one with neurovisceral lipidoses and vertical supranuclear ophthalmoplegia) had activities close to those of normal controls. These findings substantiate previous observations of low phosphodiesterase activities in NP disease and suggest that the enzymatic function affected by the NP genes includes specificity toward PG and sphingomyelin. Deficiency of PG phospholipase C may explain the accumulation of bis(monoacylglycero)phosphate in NP disease.- - - - - - - - - - ranking = 1keywords = supranuclear ophthalmoplegia, supranuclear, ophthalmoplegia (Clic here for more details about this article) |
13/19. A progressive neurologic disorder with supranuclear vertical gaze paresis and distinctive bone marrow cells.Nine patients with a progressive neurologic disorder that was characterized by mental deterioration, supranuclear vertical gaze paresis, and foam cells or sea-blue histiocytes in the bone marrow are described and compared with patients who were previously described as having " neurovisceral storage disease with vertical supranuclear ophthalmoplegia" and "dystonic lipidosis." The clinical manifestations of our patients and those described by others and the pathologic findings and profiles of lipid analysis reported by others are similar to those in patients with niemann-pick disease, type c. Sphingomyelinase activities in leukocytes and skin fibroblasts were normal in our patients and in more than half of the reported cases; these findings are also compatible with those in patients with niemann-pick disease, type c. Until the biochemical and genetic abnormalities of niemann-pick disease, type c are clearly defined, it is justifiable to classify the disorder under discussion as a subgroup of niemann-pick disease, type c because it seems to be a heterogeneous group. From the clinical point of view, the diagnosis is difficult to establish in the absence of abnormalities in the bone marrow in patients who are older than 20 years; repeat examinations of the bone marrow are necessary in such patients. Clinicians should be aware of this disorder not only in patients in the first and second decades of life, when this disorder usually becomes symptomatic, but also in patients in the fourth and fifth decades.- - - - - - - - - - ranking = 1.201302639288keywords = supranuclear ophthalmoplegia, supranuclear, ophthalmoplegia (Clic here for more details about this article) |
14/19. Juvenile Niemann-Pick disease with vertical supranuclear ophthalmoplegia. Two cases reports and review of the literature.Examination of two siblings who had histories of progressive decline in speech, intelligence, and coordination disclosed vertical supranuclear ophthalmoplegia, hepatosplenomegaly, and signs of diffuse CNS dysfunction. Niemann-Pick "foam cells" were found in the bone marrow of both patients. The features of these cases correlate in appearance and clinical findings with those of 21 other previously reported cases, which are reviewed in this article. knowledge of the clinical manifestations of this particular variety of Niemann-Pick disease should aid in its earlier diagnosis.- - - - - - - - - - ranking = 5keywords = supranuclear ophthalmoplegia, supranuclear, ophthalmoplegia (Clic here for more details about this article) |
15/19. Ocular motor signs in some metabolic diseases.Ocular motor disturbances are described with a miscellany of metabolic disturbances. Horizontal gaze abnormalities, often simulating congenital ocular motor apraxia, characterized Gaucher's disease. Vertical gaze abnormalities, especially downgaze paralysis, characterized what is generally considered a variant of Niemann-Pick disease, or sea-blue histiocytosis, but which we prefer to call the "DAF" syndrome. A form of internuclear ophthalmoplegia but with nystagmus of the adducting eye characterized abetalipoproteinemia. epileptiform eyelid and eye movements occurred in a case of methylmalonohomocystinuria. Ocular motor abnormalities are also described with variation of olivopontocerebellar degeneration and with ataxia telangiectasia.- - - - - - - - - - ranking = 0.001173127955306keywords = ophthalmoplegia (Clic here for more details about this article) |
16/19. Psychosis as the initial manifestation of adult-onset Niemann-Pick disease type C.Niemann-Pick disease type C (NPC) is a neurometabolic genetic disorder that is distinguished from Niemann-Pick disease by its later onset, more insidious progression, variable visceromegaly, and abnormalities of intracellular cholesterol metabolism. We describe a patient who presented with an 8-year history of psychosis requiring chronic neuroleptic therapy for a presumed diagnosis of schizophrenia. He was subsequently diagnosed with NPC as the emerging features of dementia, ataxia, dysarthria, and vertical supranuclear ophthalmoplegia were recognized. The characteristic features of adult-onset NPC and the obstacles to early diagnosis are reviewed.- - - - - - - - - - ranking = 1keywords = supranuclear ophthalmoplegia, supranuclear, ophthalmoplegia (Clic here for more details about this article) |
17/19. Type C Niemann-Pick disease: report of a Chinese case.We report on a 12-year-old Chinese child with type C Niemann-Pick disease, who presented primarily with neurologic symptoms. He started to develop ataxia and dysarthria at the age of six years. dementia, dysphagia, dystonia and seizures, in that sequence, followed within a couple of years. He was anarthric and bedridden five years after onset. Supranuclear vertical gaze palsy was found at the beginning of the illness. However, no hepatosplenomegaly or other physical abnormality was noted. Bone marrow aspirates revealed foamy storage cells and sea-blue histiocytes. However, sphingomyelinase activity in the cultured skin fibroblast was normal. The characteristic clinical presentations and typical pathologic and histochemical findings meet the diagnostic criteria of type C Niemann-Pick disease. We report the first Chinese case of type C Niemann-Pick disease and review 73 cases reported previously.- - - - - - - - - - ranking = 5.6883490266101E-7keywords = palsy (Clic here for more details about this article) |
18/19. adult-onset Niemann-Pick type C disease. Clinical, biochemical, and genetic study.BACKGROUND: Niemann-Pick type C disease is an autosomal recessive neurometabolic disorder of unknown origin mapped to chromosome 18q11-12 in most of the studied families. In contrast to the sphingomyelin lipidoses, in Niemann-Pick type C disease, fibroblasts are impaired in intracellular homeostatic responses to exogenous low-density lipoprotein (LDL) cholesterol. Biochemical heterogeneity of the disorder in relation to abnormal LDL processing is associated with various clinical presentations, but adult-onset Niemann-Pick type C disease is rare and has not been comprehensively characterized. OBJECTIVE: To describe clinical, biochemical, and genetic features of adult-onset Niemann-Pick type C disease in 3 siblings. DESIGN AND SETTING: Case series in a tertiary care center. patients: The 3 siblings manifested a variable combination of vertical supranuclear ophthalmoplegia, ataxia, and splenomegaly. Brain magnetic resonance imaging showed cerebellar atrophy; brainstem auditory evoked responses were unobtainable, and bone marrow examination disclosed typical foam cells. The patients were 20, 26, and 28 years old and belonged to a sibship of 13 born of consanguineous healthy parents. methods: esterification of exogenous LDL cholesterol in cultured skin fibroblasts and filipin staining for free intracellular cholesterol. polymerase chain reaction-based dna linkage study using AC microsatellite markers D18S40, D18S44, D18S480, and D18S66. RESULTS: fibroblasts of the 3 patients showed a 23% to 58% block in the induced cholesterol esterification after 4 1/2 hours and a mild to moderate accumulation of free cholesterol. dna study demonstrated linkage to the major 18q11-12 Niemann-Pick type C locus and identified unaffected carriers. CONCLUSIONS: These results confirm the diagnosis of the least biochemically affected Niemann-Pick type C phenotype in this family with adult-onset disease and support a correlation between the mild laboratory and clinical findings in this age group.- - - - - - - - - - ranking = 1keywords = supranuclear ophthalmoplegia, supranuclear, ophthalmoplegia (Clic here for more details about this article) |
19/19. Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile Niemann-Pick disease type C.A 15-year-old boy was suffering from splenomegaly and a 10-year history of a neurologic disorder that included mental retardation, vertical supranuclear gaze palsy, dysarthria, ataxia, and dystonia. Bone marrow aspirates revealed foamy cells with storage materials which were positive with filipin staining. Cultured skin fibroblasts derived from the patient showed moderate loss of sphingomyelinase activity and the impairment of cholesterol esterification. The characteristic clinical presentations and typical histochemical findings of this patient met the diagnostic criteria of Niemann-Pick disease type C (NPC). In the fibroblasts from the patient, there was an accumulation of GM2 ganglioside around their cytoplasms. Increased levels of glycolipids. including GM2 ganglioside are reported in the cerebral cortex of NPC, but not in the fibroblasts. The fibroblasts derived from NPC may reflect the abnormal metabolism of glycolipids in the central nervous system of NPC.- - - - - - - - - - ranking = 0.040261096692497keywords = supranuclear, palsy (Clic here for more details about this article) |
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