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)

Galactocerebrosidase-deficient oligodendrocytes of 'twitcher' (twi/twi) mice degenerate prematurely. Transplantation of normal bone marrow cells has been shown to alleviate symptoms and to prolong survival time. However, characteristic ataxia ('twitching') is not cured. In an attempt to improve further the condition of twitcher mice, allogeneic foetal liver cells were transplanted as a source of normal haemopoietic stem cells and supplemented with intracerebral transplantation of foetal brain cells. A reliable method was developed to detect donor-type cells in brain tissue. Bacteriophage lambda transgenic foetal mice were used as donors of both foetal liver and brain cells. Integrated copies of lambda DNA in donor cells were detected by in situ hybridization with biotinylated probes, which were then stained using streptavidin alkaline phosphatase. This technique was combined with immunohistochemistry to distinguish donor-type oligodendrocytes from macrophages. Immunoperoxidase staining with an antiserum to carbonic anhydrase-II produced dark perikarya of oligodendrocytes. The results demonstrated that local foetal brain cell grafts resulted in a wide dissemination of donor-type oligodendrocytes throughout the twitcher brain. The addition of a foetal brain cell graft to haemopoietic cell transplantation resulted in significantly prolonged survival of twitcher mice.
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PMID:Detection of migrated allogeneic oligodendrocytes throughout the central nervous system of the galactocerebrosidase-deficient twitcher mouse. 134 28

Krabbe disease is a progressive neurologic disorder caused by deficiency of the lysosomal enzyme galactocerebrosidase. The disease commonly has an early-infantile onset, but can have late-infantile, juvenile, or adult-onset phenotypes. Classic computed tomography (CT) and magnetic resonance imaging (MRI) findings in Krabbe have been well described. We report a patient, ultimately diagnosed with juvenile-onset Krabbe, who presented with atypical CT imaging and rapid disease progression. Our patient was a previously healthy and developmentally appropriate female who presented at 3 years 4 months of age with ataxia and motor regression that had progressed over the course of 6 weeks without an identifiable catalyst. CT, performed in the emergency setting, demonstrated extensive white matter hyperdensity. Subsequent MRI showed T2 hyperintensity of the white matter corresponding to the areas of hyperdensity on the CT, as well as enhancement of multiple cranial nerves bilaterally, suggestive of Krabbe disease. Enzymatic testing demonstrated low galactocerebrosidase activity and molecular testing of GALC revealed compound heterozygosity for 2 known pathogenic mutations, consistent with a diagnosis of Krabbe Disease. This included the common 30-kb deletion and a known pathogenic mutation associated with juvenile/adult-onset disease. Our patient's diffuse hyperdensity on CT offers a new radiographic finding to include in the repertoire of Krabbe imaging, and thus aide in the diagnostic evaluation. The rapidity of progression our patient demonstrated is additionally unique and should be considered in the identification of juvenile Krabbe as well as the complicated decision-making process regarding potential treatments.
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PMID:Unusual Neuroimaging in a Case of Rapidly Progressive Juvenile-Onset Krabbe Disease. 3248 59