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Background: Recent research is revealing the high rate of false-positive screening results for IEMs in the NICU population. No study published to date has specifically studied the possible relationship between nutrition and newborn screening in this population. Objective: It is suspected that NICU infants who receive PN are more likely to have abnormal newborn screening results than infants who receive EN. An understanding of the role of nutrition will assist in developing protocols for screening in the NICU and decrease false-positives. Design: Infants admitted to the NICU between January 1-June 30, 2009 were included in this retrospective chart review study (n=339). The type of nutrition and timing of its initiation was recorded and compared to newborn screening results to identify correlations with false-positives. Statistical analysis included means, percentages, Fisher's exact test, Chi-square test, and the Cochran-Mantel-Haenszel test. Results: Nutrition type was significantly associated with newborn screening (p<0.001); those who received parenteral nutrition were more likely to have a false-positive. For infants who also received PN, EN of breast milk exclusively increased risk of an abnormal screen more than formula exclusively or breast milk plus formula. The timing of parenteral nutrition had no effect on screening. Premature infants who received PN exclusively had a higher percentage of false-positives than those who received EN Conclusions: Although the hypothesis could not be statistically supported, PN appears to contribute to false-positive newborn screens. More research is needed to ascertain the role of EN and GA in newborn screening and to develop standardized protocols. / Master of Science

by Chan Chuek Kee. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 165-201). / Abstract --- p.i / Table of Content --- p.iv / List of Abbreviations --- p.viii / List of Tables --- p.x / List of Figures --- p.xii / Acknowledgement --- p.xiii / Chapter Chapter 1. --- Introduction / Chapter 1.1. --- Discovery and historical events --- p.1 / Chapter 1.2. --- General characteristics of rotavirus --- p.3 / Chapter 1.2.1. --- Virus morphology --- p.3 / Chapter 1.2.2. --- Physicochemical properties --- p.3 / Chapter 1.2.3. --- Virus stability and inactivation --- p.4 / Chapter 1.2.4. --- Genome structure --- p.4 / Chapter 1.2.5. --- Rotavirus proteins --- p.5 / Chapter 1.2.6. --- Morphogenesis --- p.8 / Chapter 1.3. --- Characteristics of rotavirus infection --- p.9 / Chapter 1.3.1. --- Morbidity and mortality --- p.9 / Chapter 1.3.2. --- Clinical features --- p.11 / Chapter 1.3.3. --- Pathogenesis --- p.13 / Chapter 1.3.4. --- Seasonal variation of rotavirus infection --- p.13 / Chapter 1.3.5. --- Nosocomial rotavirus infection --- p.14 / Chapter 1.3.6. --- Route of transmission --- p.14 / Chapter 1.4. --- Classification and epidemiology of rotaviruses --- p.15 / Chapter 1.4.1. --- Rotavirus groups --- p.15 / Chapter 1.4.2. --- Rotavirus subgroups --- p.16 / Chapter 1.4.3. --- Rotavirus serotypes --- p.17 / Chapter 1.4.4. --- Rotavirus electropherotypes --- p.20 / Chapter 1.4.5. --- "Relationship between subgroup, serotype and electropherotype" --- p.23 / Chapter 1.4.6. --- Mechanisms contributing to strain variations --- p.24 / Chapter 1.5. --- Detection of rotavirus --- p.28 / Chapter 1.5.1. --- Electron microscopy (EM) --- p.28 / Chapter 1.5.2. --- Virus isolation --- p.29 / Chapter 1.5.3. --- Serological methods --- p.30 / Chapter 1.5.4. --- RNA analysis --- p.30 / Chapter 1.5.5. --- Nucleic acid hybridization --- p.31 / Chapter 1.6. --- Prevention and control of rotavirus infection --- p.32 / Chapter 1.6.1. --- Host resistance --- p.32 / Chapter 1.6.2. --- Vaccine development --- p.33 / Chapter 1.6.3. --- Passive immunization --- p.35 / Chapter 1.7. --- Objectives of this study --- p.36 / Chapter Chapter 2. --- Materials and methods / Chapter 2.1. --- Materials --- p.38 / Chapter 2.1.1. --- Reagents for tissue culture work --- p.38 / Chapter 2.1.2. --- Reagents for electropherotyping --- p.39 / Chapter 2.1.3. --- Reagents for ELISA --- p.42 / Chapter 2.1.4. --- Reagents for hybridization assay --- p.43 / Chapter 2.2. --- Methods / Chapter 2.2.1. --- Collection of specimens --- p.46 / Chapter 2.2.2. --- Rotavirus strains --- p.46 / Chapter 2.2.3. --- Monoclonal antibodies --- p.48 / Chapter 2.2.4. --- Detection of rotavirus antigen by ELISA --- p.49 / Chapter 2.2.5. --- Rotavirus electropherotyping --- p.50 / Chapter 2.2.6. --- Serotyping of rotavirus by fluorescent foci neutralization --- p.52 / Chapter 2.2.7. --- Serotyping of rotavirus by oligo- nucleotide probes hybridization --- p.55 / Chapter 2.2.8. --- Rotavirus serotyping by ELISA --- p.59 / Chapter 2.2.9. --- Rotavirus subgrouping by ELISA --- p.61 / Chapter Chapter 3. --- Results / Chapter 3.1. --- Age and sex distribution of the study population --- p.63 / Chapter 3.2. --- Detection of rotavirus by ELISA --- p.63 / Chapter 3.3. --- Seasonal distribution of rotavirus infections --- p.67 / Chapter 3.4. --- Genetic diversity of human rotaviruses --- p.74 / Chapter 3.5. --- Subgroup determination by ELISA --- p.99 / Chapter 3.6. --- Rotavirus serotypes by fluorescent foci neutralization (FFN) --- p.102 / Chapter 3.7. --- Rotavirus serotypes by ELISA --- p.107 / Chapter 3.8. --- Rotavirus serotypes as determined by oligonucleotide probes --- p.110 / Chapter 3.8.1. --- Dot hybridization --- p.110 / Chapter 3.8.2. --- Northern blots of electrophoresed RNAs --- p.118 / Chapter 3.9. --- Temporal distribution of rotavirus serotypes --- p.124 / Chapter 3.10. --- "Association between serotype, subgroups and electropherotypes" --- p.128 / Chapter 3.11. --- Unusual rotavirus strains --- p.135 / Chapter 3.12. --- Nosocomial rotavirus infection --- p.135 / Chapter Chapter 4. --- Discussion / Chapter 4.1. --- Seasonal variation of rotavirus infection --- p.141 / Chapter 4.2. --- Molecular epidemiology of rotavirus infection --- p.143 / Chapter 4.3. --- Subgrouping of human rotavirus strains --- p.146 / Chapter 4.4. --- Serotyping rotaviruses by ELISA --- p.147 / Chapter 4.5. --- Serotyping rotaviruses by oligonucleotide probe hybridization --- p.150 / Chapter 4.6 --- Advantage and disadvantage of different methods for serotyping of rotaviruses --- p.152 / Chapter 4.7. --- Distribution of rotavirus serotypes --- p.153 / Chapter 4.8. --- Association between rotavirus serotype and electropherotype --- p.156 / Chapter 4.9. --- Nosocomial rotavirus infection --- p.158 / Chapter 4.10. --- Unusual rotavirus strains --- p.159 / Chapter 4.11. --- Concluding remark --- p.162 / Chapter 4.12. --- Future studies --- p.164 / References --- p.165

Addendum inserted at back Includes bibliographical references (leaves 266-287). 1. Introduction -- 2. Materials and general methods -- 3. Characterisation and partial purification of the lysosomal sulphate transporter -- 4. Identification of proteins involved in lysosomal sulphate transport -- 5. The relationship between a sulphate anion transporter family and the lysosomal sulphate transporter -- 6. Investigation of sulphate transport in human skin fibroblasts -- 7. Concluding remarks

Mitochondrial fatty acid �-oxidation disorders are a group of clinically and biochemically heterogeneous defects mainly associated with intolerance to catabolic stress. The diseases are potentially fatal, but treatable and the prognosis for most diagnosed disorders is generally favourable. Early diagnosis is thus important to prevent morbidity and mortality. This project describes an improved and validated quantitative fibroblast acylcarnitine profile assay for the investigation of suspected fatty acid �-oxidation disorders. Intact cells were incubated with deuterium-labelled hexadecanoate and L-carnitine, and the accumulated acylcarnitines in the medium analysed using electrospray tandem mass spectrometry. This modified procedure is less demanding technically, requires fewer cells and better reflects the in vivo acylcarnitine status than previously published methods. Mitochondrial fatty acid �-oxidation is coupled to the respiratory chain. Functional defects of one pathway may lead to secondary alterations in flux through the other. The diagnostic specificity and the prognostic potential of the in vitro acylcarnitine profile assay were investigated in fibroblasts from 14 normal controls, 38 patients with eight enzyme deficiencies of fatty acid �-oxidation presenting with various phenotypes, and 16 patients with primary respiratory chain defects including both isolated and multiple enzyme complex defects. All fatty acid �-oxidation deficient cell lines revealed disease-specific acylcarnitine profiles related to the sites of defects irrespective of the severity of symptoms or of different mutation. Preliminary studies suggested a correlation between severity of symptoms and higher concentrations of long-chain acylcarnitine species. However, the fibroblast acylcarnitine profiles from some patients with respiratory chain defects were similar to those of controls, whereas others had abnormal profiles resembling those found in fatty acid �-oxidation disorders. In vitro acylcarnitine profiling is useful for the detection of fatty acid �-oxidation deficiencies, and perhaps the prediction of disease severity and prognostic evaluation facilitating decisions of therapeutic intervention and genetic counselling. However, abnormal profiles do not exclusively indicate these disorders, and primary defects of the respiratory chain remain a possibility. Awareness of this diagnostic pitfall will aid in the selection of subsequent confirmatory tests and therapeutic options.

Addendum inserted at back / Includes bibliographical references (leaves 266-287). / xxiv, 289 leaves, [2] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2001

There is a large variety of diseases caused by single-gene mutations. Although most of these conditions are rare, together they impose a significant burden to the population. This thesis describes clinical and genetic studies of two single-gene diseases: 1) Adult-onset autosomal dominant leukodystrophy with autonomic symptoms (ADLD) caused by LMNB1 gene duplications, and characterized by autonomic, pyramidal and cerebellar symptoms. Spinal cords of patients with ADLD were studied by MRI and found to be thin, with high signal intensity in white matter. Histopathology showed loss of myelinated fibres with some reactive gliosis. DNA samples from four different families with ADLD were obtained, and the LMNB1 gene was screened for duplications. Single nucleotide polymorphism array revealed LMNB1 duplications in all ADLD families. LMNB1 mRNA and protein levels were assessed in white blood cells using quantitative polymerase chain reaction and Western blot, and increased levels of LMNB1 mRNA and lamin B1 protein could be demonstrated. We concluded that spinal cord atrophy in patients with ADLD is a valuable differential diagnostic sign, and that increased levels of LMNB1 can be detected in peripheral blood. 2) Rippling muscle disease (RMD) is caused by CAV3 gene mutations. Clinical features are percussion-induced muscle mounding, –rapid contractions and undulating muscle contractions (rippling). The CAV3 gene was sequenced in 38 members of a family with RMD. Twenty-two individuals had clinical features of RMD. No muscle weakness was seen. All patients with signs of RMD carried the p.A46T CAV3 mutation, showing that the p.A46T mutation was benign and that the diagnosis can be made clinically. In vitro contracture test results from 10 of the subjects were collected, but no association between pathological test results and RMD was found.