Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a patient with adult-onset neuronal storage disease characterized by myoclonus, cerebellar ataxia, convulsive seizures, cherry-red spots, skeletal dysplasia, mild gargoyle features, inguinal hernia, and angiokeratoma. Cytoplasmic inclusions consistent with lysosomal storage disease were demonstrated in neurons of the autonomic nervous system. Accumulation of GM3 and GM2 gangliosides was found in sympathetic ganglia but a catabolic disturbance of these gangliosides was ruled out by normal levels of GM3 ganglioside sialidase and N-acetyl-beta-hexosaminidase A activities. beta-Galactosidase activity was decreased in leukocytes and fibroblasts, but not in serum. GM1 gangliosidosis was ruled out by lipid analyses, and mucopolysaccharidosis by normal excretion of mucopolysaccharide in urine. Sialyl oligosaccharides were increased in urine and alpha-neuraminidase was deficient in fibroblasts. This disorder is considered to be an inherited metabolic disorder of sialyl glycoproteins and oligosaccharides due to deficiency of an alpha-neuraminidase.
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PMID:Adult type neuronal storage disease with neuraminidase deficiency. 53 22

Two unrelated patients with the cherry red spot--myoclonus syndrome, a rare chronic neuronal storage disorder that begins in childhood with progressive myoclonus, cherry red spots at the macula, and easily controlled seizures, but no dementia, have been investigated electrophysiologically in order to characterize the myoclonic and electroencephalographic features of this syndrome. Phenomenologically, the disease most closely resembles the Ramsay Hunt syndrome, although certain unique features are noted and the patients are not photosensitive. Pathologically and clinically, the disease is related to mucolipidosis type I and atypical cases of GM1 gangliosidosis, and the EEGs obtained from our patients are identical to those seen in mucolipidosis type I. Because of the unusual clinical picture presented in this disease, there should be no difficulty in differentiating it from other more malignant storage disorders and progressive myoclonus epilepsies of childhood. Electrophysiological findings suggest that the myoclonic jerks do not originate cortically, but the specific subcortical generators have not been identified.
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PMID:Electrophysiological studies in two patients with cherry red spot--myoclonus syndrome. 85 94

Clinical findings were compared with the results of molecular analysis in 16 Japanese patients from 10 unrelated families with the adult/chronic form of GM1 gangliosidosis. Age of onset ranged from 3 to 30 years. Major clinical manifestations were gait and speech disturbances caused by persistent muscle hypertonia. Dystonic postures and movements, facial grimacing, and parkinsonian manifestations were commonly seen. Cerebellar signs, myoclonus, severe intellectual impairment, dysmorphism, or visceromegaly were not observed. A common single-base substitution, 51Ile(ATC)----Thr(ACC), reported in a previous study of ours, was confirmed in 14 patients by the Bsu36I restriction site analysis; one was a compound heterozygote with another mutation (457Arg[CGA]----Gln[CAA]) and the others were homozygotes of this mutation. Clinically, the compound-heterozygous patient showed more severe neurological manifestations and a more rapid clinical course than those of homozygotes. The homozygotes showed considerable variations in the age of onset and subsequent clinical course. The 51Ile----Thr mutant allele expressed a significant amount of beta-galactosidase activity, whereas the 457Arg----Gln mutant allele expressed extremely low activity in human GM1 gangliosidosis fibroblasts. We conclude that these gene mutations causing different residual enzyme activities are related to the severity of clinical manifestations, but some other genetic or environmental factors contribute to clinical heterogeneity. The Bsu36I restriction site analysis was performed in 7 families and provided clear results for the diagnosis of heterozygotes as well as homozygotes of this specific clinical form of GM1 gangliosidosis. The technique is applicable to prenatal diagnosis and genetic counseling.
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PMID:GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients. 135 43

Clinical and biochemical studies are reported on a 32-year-old man with GM1 gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM1 ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM1 ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM1 ganglioside beta-galactosidase activity was only 10% of normal. These findings suggest that impaired GM1 ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM1 gangliosidosis.
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PMID:A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies. 212 25

Three adult patients in a single family showed severe myoclonus, ataxia, and pyramidal signs. Enzymatic analysis of lymphocytes, plasma, and cultured skin fibroblasts showed marked deficiency of beta-galactosidase activity, more profound with GM1 ganglioside than with another natural substrate, asialofetuin. Other lysosomal hydrolases were normal. Although the physical signs were similar to those of types 1 and 2 GM1 gangliosidosis, none had bony abnormalities.
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PMID:A family with beta-galactosidase deficiency: three adults with atypical clinical patterns. 307 94

Two young adult siblings were diagnosed as having a deficiency of acid beta-galactosidase activity in leukocytes and fibroblasts. The parents had enzyme levels approximately half of the normal level, consistent with this being the primary enzymatic lesion. Sialidose activities measured with natural and synthetic substrates in the patient's skin fibroblast cultures were normal. Hybridization of one of these patient's cells with cells from a patient with GM1 gangliosidosis, Type 1 did not show complementation of beta-galactosidase activity. However, when the cells from the patient were hybridized with cells from a patient with combined sialidase and beta-galactosidase deficiency, complementation was observed. These two siblings have ataxia, mild intellectual deterioration, slurred speech, mild vertebral changes and little, if any, visceromegaly. They do not have myoclonus, seizures or cherry-red spots, which are found in most patients with combined sialidase and beta-galactosidase deficiency. These patients are discussed with regard to other patients in the literature called variant or adult GM1 gangliosidosis.
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PMID:Adult GM1 gangliosidosis: clinical and biochemical studies on two patients and comparison to other patients called variant or adult GM1 gangliosidosis. 677 95

Clinical and pathological studies are reported from investigation of a 27-year-old man with GM1 gangliosidosis who experienced a slowly progressive dystonia that began about age 4, primarily affected the face and limbs, and eventually became almost totally incapacitating. There was only mild intellectual deterioration; myoclonus, seizures, and macular cherry-red spots were never observed. Postmortem examination revealed intraneuronal storage, localized predominantly to the basal ganglia, in which neurons contained round, multilamellated inclusions. Golgi studies revealed meganeurites arising from medium spiny neurons. Other areas of the central nervous system appeared relatively unaffected, although small basilar dilatations were observed in scattered cortical pyramidal neurons and Purkinje cell dendrites showed focal swellings. Vacuolated cells of the reticuloendothelial system were observed, including Kupffer cells and histiocytes in the spleen, marrow, and intestinal tract. Biochemical analysis revealed a generalized beta-galactosidase deficiency with specific accumulation of GM1 ganglioside in the basal ganglia.
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PMID:Chronic GM1 gangliosidosis presenting as dystonia: I. Clinical and pathological features. 679 74

Thirteen patients with galactosialidosis (beta-galactosidase-neuraminidase deficiency) from 9 families including two autopsy cases were studied from clinical, genetic, cytological and biochemical standpoints. Coarse facies, myoclonus, cerebellar ataxia, angiokeratoma, loss of vision, corneal opacity and cherry-red spots were the main signs and symptoms although these clinical manifestations were widely variable in individual cases. It is not yet known whether these clinical variations represent genetic heterogeneity or not. Deficiency of beta-galactosidase and neuraminidase was the most prominent biochemical abnormality in this disease. Beta-Galactosidase activity was restored in fibroblasts when serine-thiol protease inhibitors were added to the culture medium. Cathepsin B activity was significantly high in fibroblasts, liver and brain from the patients. It was demonstrated that neuraminidase was susceptible to the procedures for disrupting cells and tissues, such as sonication and freezing. The stability of this enzyme may be dependent on the molecular state in relation to cell membranes.
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PMID:Galatosialidosis (beta-galactosidase-neuraminidase deficiency): clinical and biochemical studies on 13 patients. 681 2