Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the course of investigating a 10-year-old boy because of progressive deterioration of intellectual functioning, ataxia, and hemiplegia, an absence of serum hexosaminidase activity was noted. A skin biopsy examined by electron microscopy showed axonal accumulations of dense osmiophilic deposits. Because of the patient's age at onset and the slowly progressive nature of his ilness, we are reporting an atypical juvenile case of Sandhoff disease.
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PMID:Progressive cerebellar ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10-year-old child: juvenile Sandhoff disease. 55 67

A boy with mild hand tremor since age 2 1/2 was found at 4 to have cherry-red spots and mild trucal ataxia without seizures or dementia. Biochemically, he had striking hexosaminidase deficiency (serum: 4.6 percent of normal, 88.9 percent heat-labile; leukocyte: 2.2 percent of normal, 84.6 percent heat-labile; fibroblast 12.8 percent normal, 93.1 percent heat-labile). The residual hexosaminidase activity migrated electrophoretically in two bands. The major band comigrated with hexosaminidase A, the minor with hexosaminidase S. Hexosaminidase B was totally absent. The parents had partially reduced hexosaminidase with a decreased heat-stabile fraction. This disorder may result from a new mutation closely related to that causing Sandhoff-Jatzkewitz disease.
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PMID:A new juvenile hexosaminidase deficiency disease presenting as cerebellar ataxia. Clinical and biochemical studies. 56 95

Abnormality in the beta-hexosaminidase alpha gene underlying the clinical phenotype of a Lebanese patient with a juvenile form of Tay-Sachs disease has been studied. Clinical features were progressive spasticity, ataxia, and cognitive decline. The protein coding sequence of several beta-hexosaminidase alpha-chain complementary DNAs isolated by polymerase chain reaction was completely normal except for a G-to-A transition at nucleotide position 1511 within exon 13, which resulted in substitution of the normal arginine 504 (CGC) with histidine (CAC). Although the patient was from a first-cousin marriage, she was heterozygous for this mutation. The abnormality in the other allele, which is carried by the father, was not identified, except that it is neither of the two mutations responsible for the infantile Jewish Tay-Sachs disease. Biosynthetic and immunoprecipitation studies in cultured fibroblasts showed synthesis of the alpha-chain precursor, but the mature form of the alpha-subunit was not detected.
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PMID:Genetic cause of a juvenile form of Tay-Sachs disease in a Lebanese child. 199 72

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.
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PMID:Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias. 227 Jul 51

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.
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PMID:Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias. 228 45

A girl aged 12 y, 9 mo, suffered from a progressive neurodegenerative disorder marked by ataxia, extrapyramidal symptoms, and convulsions. A skin biopsy showed axonal pathology that emphasized axonal segments enlarged by mitochondria, dense bodies, and lysosomal residual bodies of the membranous cytoplasmic body type. This ultrastructural pathology suggested GM2 gangliosidosis which was shown to be a B1 variant by specific biochemical studies, although conventional techniques had failed to detect GM2 gangliosidosis. The B1 variant is marked by a deficient activity of beta-hexosaminidase A towards one substrate, and by an almost normal activity towards another. Both parents showed a diminished activity towards the sulfated substrate, suggesting a heterozygous state, and almost normal activity with the second substrate type.
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PMID:B1 variant of GM2 gangliosidosis in a 12-year-old patient. 252 32

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

We have measured in leukocytes the following lysosomal enzymes in 11 Friedreich disease cases, 11 "atypical" recessive ataxias, 13 neurological controls and 16 normal controls: hexosaminidase A and B; beta-galactosidase and neuraminidase (labile and cold stable, or A and B). The lysosomal enzyme deficiencies known to produce certain forms of spinocerebellar degeneration were not present in Friedreich's disease or the Charlevoix-Saguenay syndrome. The very small scale survey of "atypical" recessive ataxias revealed 3 cases of severe deficiencies in hexosaminidase activity. Two adult brothers presenting with the clinical phenotype of Kugelberg-Welander disease (one also with ataxia), were shown to have a severe deficiency of both HEX A and HEX B activity (Sandhoff biochemical pattern). This is the first such report. A further adult female patient, unrelated to the others, had a severe isolated deficiency of HEX B and presented with a very slowly progressive and mild ataxia with severe internal strabismus. These patients and their families are being studied clinically and biochemically in greater detail and will be reported elsewhere. However these preliminary findings justify screening for such lysosomal defects in all cases of "atypical" recessive ataxia.
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PMID:Lysosomal enzymes in ataxia: discovery of two new cases of late onset hexosaminidase A and B deficiency (adult Sandhoff disease) in French Canadians. 623 79

A progressive spinocerebellar degenerative disorder was characterized in nine patients, aged 11 to 37 years, from four unrelated Ashkenazi Jewish families; affected individuals had markedly deficient beta-hexosaminidase A activity. Symptoms included early onset of cerebellar signs (tremor, incoordination, and dysarthia) and, with maturity, the development of upper and lower motor neuron disorders, marked dysarthia, and ataxia. Three older patients, aged 26, 32, and 37 years, had dementia or recurrent psychotic episodes. Membrane-bound lamellar cytoplasmic inclusions, consistent with lysosomal ganglioside accumulation, were observed in rectal ganglia. The activity of beta-hexosaminidase A was markedly deficient in all sources analyzed. Parents had activities consistent with heterozygosity, confirming autosomal-recessive transmission of the beta-hexosaminidase A-deficient gene and the adult variant disorder. Residual beta-hexosaminidase A activity, partially purified by anion-exchange chromatography from cultured skin fibroblasts of the affected individuals, was heat-labile and co-electrophoresed with normal beta-hexosaminidase A. These findings suggest that these patients were allelic for a new beta-hexosaminidase A mutation and may represent a genetic compound of this allele and the allele causing Tay-Sachs disease.
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PMID:Chronic GM2 gangliosidosis masquerading as atypical Friedreich ataxia: clinical, morphologic, and biochemical studies of nine cases. 645 83

A 3-year-old boy developed progressive neurological deterioration in his third year, characterized by dementia, ataxia, myoclonic jerks, and bilateral macular cherry-red spots. Hexosaminidase A (HEX A) was partially decreased in the patient's serum, leukocytes, and cultured skin fibroblasts. Hexosaminidase was studied in serum and leukocytes from family members. Four members of the paternal branch appeared to be carriers of classical infantile Tay-Sachs allele, HEX alpha 2, probably receiving the gene from one great-grandparent of Ashkenazi origin. In the maternal branch, no one was a carrier of classical infantile Tay-Sachs disease, but five individuals were carriers of a milder alpha-locus defect. The patient, therefore, was a genetic compound of two different alpha-locus hexosaminidase mutations. At least 21 families with late-infantile or juvenile GM2 gangliosidosis have been reported, 18 of them with alpha-locus mutations, and three with beta-locus mutations. Genetic compounds of hexosaminidase have been reported in at least seven families, five with alpha-locus mutations and two with beta-locus mutations. The compound had the phenotype of infantile Tay-Sachs disease in one family, infantile Sandhoff disease in another, and the normal phenotype in the rest.
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PMID:Alpha-locus hexosaminidase genetic compound with juvenile gangliosidosis phenotype: clinical, genetic, and biochemical studies. 677 23


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