3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item The Phenotype of Huntington’s disease like 2(2020) Anderson, David GrahamBackground: Huntington’s disease like 2 (HDL2) is described as the disease with the greatest resemblance to Huntington’s disease (HD). Both disorders clinically comprise a movement disorder, dementia and psychiatric symptoms. HDL2 has been reported exclusively in people of African ancestry, with the highest frequency in South Africa. Anecdotally, HDL2 has been associated with acanthocytes on blood smears, less oculomotor dysfunction and greater parkinsonism, potentially differentiating it from HD. Aim: To describe systematically the HDL2 phenotype and compare it to that of HD. Method: A systematic review of published HDL2 clinical descriptions was conducted to establish the extant HDL2 phenotype. Subsequently, a blinded cross-sectional observational study compared African ancestry subjects. HDL2 (n=15) study participants were compared to subjects with HD (n=13); these two groups were concurrently compared to an unaffected control group. Data collected included a standardised history, general and neurological examination results, blood samples and MRI scans. Motor rating scales were used to assess the movement disorder of affected subjects which was video-recorded. The data were analysed with respect to clinical phenotypes, quantitative radiological volumes and erythrocyte features. Results: The literature generally described the HDL2 phenotype as similar to HD, however, HDL2 subjects were reported to have less oculomotor dysfunction, dystonia, dysarthria and greater parkinsonism. Only four HDL2 cases had reported acanthocytes. The current study found no acanthocytes in HDL2 or any other participants. The MRI intracerebral volumes of subjects with HDL2 and HD showed similar cortical and subcortical atrophy but the thalamic volumes in subjects with HDL2 were smaller than those of the HD groups. Blinded raters could not distinguish between HDL2 and HD after analysing individual subjects. The two affected groups had similar overall Unified Huntington’s Disease Rating Scale (UHDRS) motor scores, with worse scores for some of the motor and cognitive components in the HDL2 group. Conclusion: This research suggests that HDL2 and HD cannot be differentiated based on the presence of acanthocytes or by examining individual patients. The study shows that there is a predominant clinical similarity between HDL2 and HD, however, there are additional findings that suggest HDL2 has clinical and radiological features that are more severe. This finding may have implications for the pathogenic mechanisms of both diseases. Furthermore, this research has found potential clinical and neuroimaging biomarkers for HDL2 that may give reference for future research into the pathogenesis and treatment of HDL2Item Can one develop a biomarker to detect movement disorder types?(2017) Kim, KimoonThis study presents the development of a potentially new biomarker for three different movement disorders: Huntington’s Disease (HD), Parkinson’s Disease (PD) and Essential Tremors (ET). A Leap Motion® gaming device was used to record the trajectories of subjects’ forefinger as they trace simple patterns in the air. The patterns used were stepfunction, triangle and circle. The recorded signals were analysed using transform functions and Fourier analysis. Both analysis types yielded features from which differences between the four categories studied: PD, HD, ET and control subjects, were sought and displayed in both graphical and numerical forms. The X-axis and Y-axis of the signals were separately analysed and yielded different results. For the step-function pattern, no distinct differences between the four categories were found from the transfer function analysis whereas the Y-axis of the signal could distinguish between the categories. For the triangle pattern, the X-axis features provided a discrimination between the categories while the Y-axis feature did not. For the circle pattern, neither X-axis nor Y-axis features were able to distinguish between the categories. A Fourier analysis showed a better discrimination ability for both X- and Y- axis. This study is a preliminary one and all results indicate that more subjects of all categories are needed to develop a bio-marker for the diseases studied and that a higher order transfer function analysis is required. However, the methodology outlined in this work, comprising of both the experimental system and the analysis showed a potential to produce a biomarker for movement disorders.Item The utilization and outcome of diagnostic, predictive and prenatal genetic testing for Huntington disease in Johannesburg from 1998 to 2006(2009-05-11T08:04:01Z) Sizer, Elaine BernadeneABSTRACT Huntington Disease (HD) is a neurodegenerative disorder that is inherited in an autosomal dominant manner, and for which testing is available. The aim of this retrospective file-based study was to analyse the numbers and demographics of individuals who had diagnostic, predictive or prenatal genetic counselling and/or testing for HD between January 1998 and December 2006 through the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg. Files for 287 individuals who had genetic counselling and/or testing for HD were included in this study, with 77% being diagnostic cases, 20% predictive and 3% prenatal. When the results obtained in this study were compared to a study by Kromberg et al. (1999) done previously in the same Division, it was found that there has been an increase in the number of diagnostic and predictive tests done per year during this study, with diagnostic tests making up a greater percentage of the total number of tests performed. One of the objectives of this study was to characterise the individuals who requested HD testing and to compare the characteristics of those in the diagnostic testing group to those in the predictive testing group. The median age of the individuals in the predictive testing group was 30 years, which was significantly different from the median age of 49 years for individuals in the diagnostic testing group (p<0.001). It was found that there were significantly more women than men requesting predictive testing (p=0.02), while the number of males and females in the diagnostic testing group was similar (p=1.00). There was also a greater percentage of employed (76.4%) versus unemployed (23.6%) individuals in the predictive testing group, while the percentages of employed and unemployed individuals in the diagnostic testing group were similar (45.5% and 54.5% respectively). Significantly more individuals in the diagnostic testing group had children (74.5%) compared to those in the predictive testing group, where 44.6% of individuals had one or more children. There was a greater percentage of white individuals in the predictive testing group (91% white; 3.5% black) compared to the diagnostic testing group (48% white, 42% black). The completion rate of the predictive testing process was 66.7%. In the predictive testing group, 39.5% of individuals tested positive for HD, and in the diagnostic testing group 53% of individuals tested positive for HD. Nine prenatal tests were requested by five different couples, and 7 tests were performed. Three of these fetuses tested positive for HD (including a set of twins) and these two pregnancies were terminated. Overall, there seems to be a lack of awareness of and/or access to the genetic services offered for HD through the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, particularly among black individuals and the professionals treating them. Information generated from this study can be used to understand the individuals seeking genetic counselling and/or testing for HD better, and can direct efforts to improve awareness and access amongst groups noted to be under-represented. It also serves as a starting point for further research.