Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Hexosaminidase deficiency diseases or GM2-gangliosidoses were originally described as infantile encephalopathies. Recently, hexosaminidase deficiencies have been found with different phenotypes, including juvenile and adult encephalopathies, cerebellar ataxias, and motor neuron diseases. Individual cases have resembled Ramsey-Hunt syndrome, olivopontocerebellar ataxia, Friedreich ataxia, amyotrophic lateral sclerosis, Kugelberg-Welander disease, Fazio-Londe disease, and Charcot-Marie-Tooth disease. Tremor, dystonia, spastic paresis, and psychosis have been seen. Since few diagnosable causes for these system atrophies are known, these patients should be tested for hexosaminidase deficiency. These recessive disorders fit a multiple loci/multiple alleles genetic scheme, and a clinical genetic classification is presented.
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PMID:The clinical spectrum of hexosaminidase deficiency diseases. 719 92

The many conventional classifications of cerebellar degeneration are usually based on information obtained in post-mortem examinations. On the other hand, neuroimagings, particularly with follow-up imaging studies, can demonstrate morphologic changes at various stages of disease evolution in living patients, thus providing a better understanding and evaluation of the disease processes, leading towards an earlier and more accurate diagnosis. Obviously, some patients require determination of a biochemical marker or markers in the final diagnosis. In Friedreich's ataxia, major changes are severe atrophy of the spinal cord with flattening of its posterior aspect. The medulla oblongata becomes smaller and the vermian and paravermian structures adjacent to the primary fissures become mildly atrophic. In hexosaminidase deficiency, there is pancerebellar atrophy with marked dilatation of the fourth ventricle. Cerebellar atrophy is more marked in the hemispheres than in the vermis, while the brain stem shows little change. The frontal and parietal sulci are usually slightly prominent. In cerebello-olivary atrophy (also called cortical cerebellar degeneration), there is atrophy of the superior vermis, especially the declive, folium and tuber. There is also atrophy of the lateral part of the cerebellar hemispheres, giving an appearance of the "fish-mouth deformity" on parasagittal sections. The fourth ventricle may be greatly enlarged. In dominant olivopontocerebellar atrophy (OPCA), the Menzel type is characterized by cerebellar atrophy of the "fine comb" type with the greatest involvement in the anterior lobe and in the upper part of the middle lobe. The hemispheres are more involved than the vermis. The brainstem, especially the pons, and the brachia pontis are also atrophic. In severe cases, the changes are very marked. Although the fourth ventricle is large, it lacks the ballooning characteristic of OPCA with slow saccades. In OPCA with slow saccades with or without retinal degeneration, the most pathognomonic features are "ballooning of the fourth ventricle" due to excavation of its floor and the "molar tooth deformity" secondary to severe atrophy of the pons, brachia pontis and conjunctiva. The cerebellum usually shows pancerebellar atrophy of the "fine comb" type. In recessive OPCA, cerebellar atrophy is most marked in the lateral part of the cerebellar hemispheres with "fish mouth deformity" secondary to drop-out of the tertiary and secondary folia from the primary folia. This feature is less marked in cases of atypical cerebello-olivary atrophy. In late-onset sporadic OPCA with autonomic failure, the cerebellum, especially its lateral portions and the brainstem, are variably involved in the atrophic processes, ranging from very mild to severe involvement.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:MRI and CT features of cerebellar degeneration. 810 35