Lactosylceramide galactosidase: Comparison with other sphingolipid hydrolases in developing rat brain

Four enzyme assays were carried out with brains from rats of age 4 days to about 320 days. The enzymes were acid hydrolases: lactosylceramide galactosidases, galactosylphenol galactosidase, glucosylceramide glucosidase,a nd sphingomyelin phosphocholine hydrolase. The first two activities (based on wet brain weight) rose with age until about 24 days, then declined moderately; this curve parallel somewhat the curve for ganglioside concentration in brain. It is suggested that this parallelism supports the idea that lysosomal enzymes function in normal turnover. The other two enzymes studied showed a steadily declining activity with increasing age. It was found that the brain cytosol contained 12% or less of the galactosidase activiti, the value increasing somewhat in older rats. Most of the particulate galactosidase activities could be dispersed by sonication. The similarities between the two galactosidase activities suggest that most of the hydrolysis of the galactosylphenol is carried out by the lactosylceramide hydrolase. A procedure is given for preparing [3H]lactosylceramide labeled in the galactose portion of the molecule and for the assay of its hydrolase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32942/1/0000325.pd

A new severity score index for phenotypic classification and evaluation of responses to treatment in type I Gaucher disease

Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment.The \u201cGaucher Disease Severity Score Index Type I\u201d(GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods. Siix specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available. It is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment

Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.</p> <p>Methods</p> <p>We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100^threpetitive reading, 2) rate of change, 3) average of 60–110^threading and 4) overall average of all readings.</p> <p>Results</p> <p>All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.</p> <p>Conclusion</p> <p>The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.</p

The Saccadic and Neurological Deficits in Type 3 Gaucher Disease

Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8–28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials