Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two adult Ashkenazi Jewish siblings have had slowly progressive deterioration of gait and posture since early childhood, distal to proximal muscle atrophy, pes cavus, foot drop, spasticity, mild ataxia of limbs and trunk, dystonic features, and dysarthria. Vision and optic fundi are normal, verbal intelligence is stable, and no seizures have occurred. The sister of the patients died at 16 years of age with the same illness. Autopsy showed diffuse neuronal storage, predominating in subcortical areas, consisting of membranocytoplasmic bodies, zebra bodies, and complex lamellar structures. GM2 ganglioside was increased in her brain. Hexosaminidase A was decreased in serum and leukocytes of the living patients, and was in the range for carriers of Tay-Sachs disease in their parents. The disease found in this family represents a new, more indolent variant of GM2 gangliosidosis.
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PMID:Adult (chronic) GM2 gangliosidosis. Atypical spinocerebellar degeneration in a Jewish sibship. 17 70

Two sisters presented with progressive muscle cramps, as well as wasting and weakness of the legs with onset after age 20. They also showed intention tremor of the upper extremities and dysarthria starting during the first decade. The older patient also had fasciculations; the younger, hyperreflexia. Total plasma beta-hexosaminidase (Hex) activity with 4-methylumbelliferyl-acetyl-glucosamine as substrate was reduced to 1.4% and 2.7% of the control in the 2 patients, respectively. Hex A activity measured by 4-methylumbelliferyl-N-acetylglucosamine-6-O-sulphate as substrate was 9.9% and 12.8% of the mean control value in the 2 patients, respectively. Hex B activity was undetectable in both patients. Leukocyte total Hex activity was 7-8% of normal; residual Hex A activity in the 2 patients was 17.8% and 16.3% of normal controls, respectively. Fibroblastic residual Hex A activity in the 2 patients was 9.6% and 22% of normal mean value, respectively. Appendiceal ganglion cells contained membranous cytoplasmic bodies in the younger patient. Thin layer chromatography of the appendiceal extract from one patient (III/2) showed a marked increase of GM2 ganglioside, and some increase of GM3 ganglioside. Northern blots performed on fibroblast cell lines from both patients for the demonstration of alpha and beta locus messenger RNA showed no difference between patients and control. These patients have a rare form of adult-onset progressive motor neuron disease presumably due to abnormal beta subunits, causing severe deficiency of both Hex A and Hex B. The phenotypic expression of this disease is similar to motor neuron disease due to alpha locus mutations, which suggests that the Hex A deficiency, even though only a partial one, may be the important pathogenic factor.
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PMID:Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency. 297 15

The authors report on a Portuguese family with 3 adult brothers affected with GM2-gangliosidosis (B1 variant) in a sibship of 4, and more specifically on one of these brothers with neurological onset at the age of 17. Psychosis, lower motoneuron involvement and dysarthria were predominant in two of the cases; the third had a cerebellar symptomatology. Hexosaminidase A activity, studied in leukocytes, was profoundly deficient when measured using the specific sulfated substrate, but nearly normal using a conventional assay (non-sulfated substrate). These results established the diagnosis of the unusual enzymological form of GM2-gangliosidosis known as the B1 variant, which had so far not been associated with an adult phenotype. Molecular studies are in progress to study genotype/phenotype correlations in this family in comparison with known mutations in the B1 variant and in adult GM2-gangliosidosis. This report also emphasizes that a metabolic etiology, leading to genetic counselling, should be considered in some familial degenerative neurological disorders.
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PMID:[GM2-Gangliosidosis variant B1 disclosed during adolescence by an isolated multi-systemic involvement of the central and peripheral nervous systems]. 780 Oct 43

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.
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PMID:Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile Niemann-Pick disease type C. 954 79

We report a case of amyotrophic lateral sclerosis (ALS) with IgM antibody against gangliosides GM2 and GD2. A 57-year-old woman presented with slowly progressive muscular weakness of the upper extremities and dysarthria. She fulfilled the clinical and electrophysiological criteria of ALS, and died from sudden suffocation about 3 years after the onset of illness. The patient's serum IgM antibody was shown to recognize the structure shared by GM2 and GD2. Since anti-GM2 antibodies have been implicated in motor neuropathy or motor neuron syndrome, this rare case might contribute to the understanding of the immunological aspects of ALS.
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PMID:Amyotrophic lateral sclerosis with IgM antibody against gangliosides GM2 and GD2. 1270 85

Late-onset Tay-Sachs (LOTS) disease is a chronic, progressive, lysosomal storage disorder caused by a partial deficiency of beta-hexosaminidase A (HEXA) activity. Deficient levels of HEXA result in the intracellular accumulation of GM2-ganglioside, resulting in toxicity to nerve cells. Clinical manifestations primarily involve the central nervous system (CNS) and lower motor neurons, and include ataxia, weakness, spasticity, dysarthria, dysphagia, dystonia, seizures, psychosis, mania, depression, and cognitive decline. The prevalence of peripheral nervous system (PNS) involvement in LOTS has not been well documented, but it has traditionally been thought to be very low. We examined a cohort of 30 patients with LOTS who underwent clinical and electrophysiologic examination, and found evidence of a predominantly axon loss polyneuropathy affecting distal nerve segments in the lower and upper extremities in eight patients (27%).
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PMID:Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients. 1864 77