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)

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

We studied three patients from two unrelated families with adult hexosaminidase A deficiency. A 30-year-old, non-Jewish proband in the first family had juvenile amyotrophic lateral sclerosis that evolved to mild dementia, ataxia, and axonal (neuronal) motor-sensory peripheral neuropathy. A 36-year-old Jewish proband in the second family had "pure" spinal muscular atrophy. One supposedly healthy brother of the first proband was found to have borderline IQ, mild spasticity, and ataxia but no evidence of motor neuron disease. Marked cerebellar atrophy was detected by head scans in all three patients. In both probands electromyograms were characterized by prominent, complex repetitive discharges in many muscles. Hexosaminidase A activities against the artificial substrate were similar to those reported in infantile Tay-Sachs disease; however, the hexosaminidase A level against GM2 substrates was higher than that found in infantile Tay-Sachs disease. The hexosaminidase A levels of the parents were in the heterozygous range. Motor neuron disease in our patients and in those previously described appears to be part of a multisystem degeneration of the nervous system.
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PMID:Motor neuron disease and adult hexosaminidase A deficiency in two families: evidence for multisystem degeneration. 315 34

Two sibling from a consanguineous Puerto Rican marriage were found to have a juvenile-onset type of lipidosis first noted at age 2 1/2 by expressing difficulties with motor function and developmental delay. They continued to deteriorate, showing muscle atrophy, spasticity, and loss of speech, and death occurred at ages 7 and 8. Examination of the brains from these patients revealed that the concentration of GM2 ganglioside was about 56% of the total gangliosides. Hexosaminidase and percent hexosaminidase A (HEX A) and other lysosomal enzymes were normal in cultured skin fibroblasts, liver, and brain. The concentration of the activator protein required for the enzymatic hydrolysis of GM2 ganglioside was in high normal levels in the brain of the patient available. However, the HEX A from the patient's brain and liver as well as from skin fibroblast lysates could not be activated to hydrolyze GM2 ganglioside by the activator protein from a control or himself. The HEX A from a control could be activated by the activator protein from controls or this patient. These patients appear to have a defect in HEX A, which does not affect it heat stability, electrophoretic migration, and activity toward fluorogenic substrates, but may affect the binding of the activator protein required for GM2 ganglioside hydrolysis. We propose to call these patients the AMB variant of GM2 gangliosidosis to denote the mutation in HEX A but with normal levels of HEX A and B with synthetic substrates. This is to distinguish these patients from those missing the activator protein and normal HEX A and B levels.
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PMID:Juvenile GM2 gangliosidosis (AMB variant): inability to activate hexosaminidase A by activator protein. 622 17