EVALUATION OF THE EFFECTIVENESS OF EXPANDED NEWBORN SCREENING BY TANDEM MASS SPECTROMETRY
Funder
National Health and Medical Research Council
Funding Amount
$375,250.00
Summary
Newborn babies in Australia are routinely tested for certain treatable disorders. Testing began in the 1960's with systematic testing for phenylketonuria, a rare amino acid enzyme defect. It causes severe mental retardation which can only be prevented if treatment is begun in the first few weeks of life. By 1997, only three other disorders, congenital hypothyroidism, cystic fibrosis, and galactosaemia, had been added to the testing protocol as tests became available. Using the new technology of ....Newborn babies in Australia are routinely tested for certain treatable disorders. Testing began in the 1960's with systematic testing for phenylketonuria, a rare amino acid enzyme defect. It causes severe mental retardation which can only be prevented if treatment is begun in the first few weeks of life. By 1997, only three other disorders, congenital hypothyroidism, cystic fibrosis, and galactosaemia, had been added to the testing protocol as tests became available. Using the new technology of tandem mass spectrometry (MSMS) it is now possible to screen for up to 30 extremely rare, treatable metabolic disorders simultaneously and cheaply, but it is not clear how effective this is. A formal trial of MSMS screening, randomly assigning babies to be tested or not tested, does not seem feasible because of the rarity of the individual disorders (most with a birth prevalence much less than 1: 50,000). Huge numbers would be needed in the trial for statistical significance. We began MSMS screening in NSW April 1998 and in South Australia in February 1999. Victoria is proposing to start screening now, but there are as yet no plans for this screening in the other states. We would like to assess the effectiveness of MSMS newborn screening using the best possible evidence drawn from all data available in the whole of Australia. We plan to undertake an economic evaluation, comparing costs and benefits such as development, hospitalisations, medical complications and other outcome measures, in screened and unscreened babies and also assess harms from screening. Because only 6 specialised laboratories in Australia, in Brisbane (2), Sydney, Melbourne, Adelaide, and Perth can diagnose these disorders, we are confident that we know of all diagnosed cases of the disorders in question. We hope to be able to show whether or not there is a benefit to affected babies by implementing newborn screening tests for these rare diseases.Read moreRead less
Implementation Of A New, Inexpensive And High-throughput Matrix Assisted Laser Desorption / Ionization _ Time Of Flight Mass Spectrometry Test For Superior Detection Of Fragile X Syndrome In Targeted Diagnostics And Newborn Population Screening.
Funder
National Health and Medical Research Council
Funding Amount
$254,175.00
Summary
Background: The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability. There are now a number of treatments for FXS. However, often this disorder is not clearly recognized. We have developed a novel FXS test that could resolve this issue. Our objective is to develop a commercial package that describes suitability of our test for diagnostic use. If successful this could potentially leading to improvement in the prognosis for FXS children through early treatment int ....Background: The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability. There are now a number of treatments for FXS. However, often this disorder is not clearly recognized. We have developed a novel FXS test that could resolve this issue. Our objective is to develop a commercial package that describes suitability of our test for diagnostic use. If successful this could potentially leading to improvement in the prognosis for FXS children through early treatment intervention.Read moreRead less
Significance Of Low-level Mosaicism To Intellectual Disability In Paediatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$483,402.00
Summary
My vision for the next 4 years is to improve outcomes for children and their families with inherited disorders associated with intellectual disability (ID) and autism through earlier diagnosis and intervention. This is of great importance with annual costs of ID close $14.72 billion to the Australian health system, and missed or delayed diagnoses being a significant problem, as ID is found in 1.7% of births, where a specific cause is currently identified in less than half.
Characterization Of A Novel Epigenetic Boundary And Long Range Epigenetic Modifications Specific To FMR1 Expansion Carriers With Behavioural And Cognitive Disorders - Implications For Earlier Diagnosis And Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$670,836.00
Summary
Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and autism and is caused by a faulty switch in the gene FMR1. We have discovered new DNA regions important in FXS. The project aims to explain how these new regions regulate the FMR1 gene. This is essential for the discovery and validation of new avenues for earlier diagnosis, treatments and therapies for children and adults with FMR1 disorders and also for informing reproductive decisions.
Infant Thyroid Hormone Levels And Long-term Child Educational Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$149,782.00
Summary
Adequate levels of newborn thyroid hormones are essential for brain development.Newborn screening for thyroid hormone deficiency ensures early identification, treatment & prevention of severe intellectual disability.But there is clinical uncertainty in mildly abnormal levels.We will assess thyroid hormone levels & subsequent educational outcomes in 1.5M Australian babies.There is potential to identify infants who, without treatment, may suffer longterm disability & lower educational achievement
Infant Thyroid Hormone Levels And Long-term Child Educational Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$490,495.00
Summary
Adequate levels of newborn thyroid hormones are essential for brain development.Newborn screening for thyroid hormone deficiency ensures early identification, treatment & prevention of severe intellectual disability.But there is clinical uncertainty in mildly abnormal levels.We will assess thyroid hormone levels & subsequent educational outcomes in 1.5M Australian babies.There is potential to identify infants who, without treatment, may suffer longterm disability & lower educational achievement
Nigel G Laing, NH&MRC Principal Research Fellowship: Neurogenetics – Gene Discovery, Pathobiology, Novel Therapeutics, Novel Diagnostics And Translation.
Funder
National Health and Medical Research Council
Funding Amount
$880,454.00
Summary
My Fellowship will expand my work identifying diseases genes for genetic muscle and nerve diseases by using new technologies that allow discovery of human disease genes which could not be found before. In addition, since we now have proof from mouse studies that heart actin is a target for therapy for the group of diseases that we discovered caused by mutations in the muscle actin protein, we shall take further steps towards making this therapy a reality for patients.
A SYSTEMS BIOLOGY APPROACH TO SCREENING, DIAGNOSIS AND PROGNOSIS FOR LYSOSOMAL STORAGE DISORDERS
Funder
National Health and Medical Research Council
Funding Amount
$900,781.00
Summary
Lysosomal storage disorders (LSD) are inherited and, at present, can only be detected in children after symptoms are obvious. We are developing newborn screening for LSD to detect affected babies before the onset of irreversible symptoms. As most LSD babies appear normal at birth it is important to be able to predict disease severity or rate of disease progression; this will help doctors know when to give therapy, which therapy is best and provide families with appropriate genetic counseling.
T Cell PKC Expression As A Novel Neonatal Predictor And Modulator Of Allergic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
This application will further assess the role of a novel biological predictor of allergic disease, which appears more accurate than any previous marker (based on preliminary data). This is highly relevant to development of predictive tools that could be ultimately used in clinical practice. We will also assess this marker as a potential target for disease prevention, as our preliminary data also indicates that it can be modified by an early intervention aimed at preventing allergic disease.
PROTEIN PROFILING FOR THE IDENTIFICATION AND MONITORING OF LYSOSOMAL STORAGE DISORDERS AND OTHER NEUROLOGICAL DISEASES
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Lysosomal storage disorders (LSD) are a group of more than 45 progressive genetic diseases, that result from the absence or impaired function of a specific enzyme in each of the body's cells. Lysosomes rid the cell of excess waste. Impaired enzyme function halts this process and waste begins to accumulate (or 'store') in the cell. Disease severity and patient longevity is variable, but severely affected patients often die by their mid-teens. LSD can affect the skeleton and joints, respiratory an ....Lysosomal storage disorders (LSD) are a group of more than 45 progressive genetic diseases, that result from the absence or impaired function of a specific enzyme in each of the body's cells. Lysosomes rid the cell of excess waste. Impaired enzyme function halts this process and waste begins to accumulate (or 'store') in the cell. Disease severity and patient longevity is variable, but severely affected patients often die by their mid-teens. LSD can affect the skeleton and joints, respiratory and cardiovascular systems, the brain, the eyes, the ears and the airways. As affected children become older, symptoms worsen. Patients often require frequent hospitalisation, and medical and surgical intervention. Approximately 10 to 15% of the general population are affected or carriers of an LSD. In Australia, one LSD child is born in every 5,000 live births. Diagnosis often takes several years, and families often have other children before their affected child is diagnosed. LSD are, therefore, a considerable burden to not only the families but also to the health care system. The goal of the Lysosomal Diseases Research Unit is Diagnosis at birth and effective therapy for lysosomal storage disorders. To this end we have been working toward the development of a newborn screening program for LSD and improved methods for the diagnosis and monitoring of therapy in this group of diseases. In this project we propose to develop and evaluate the use of protein profiling (looking at many diagnostic markers at the same time) to achieve these goals. The technology developed in this project will have potential application beyond LSD. Lysosomal dysfunction has been implicated in Alzheimer's disease and Parkinson's disease; in addition lysosomal proteins are reported to be involved in the spread of some cancers and may be useful markers for early detection. We will collaborate with other research groups to further develop protein profiling in these areas.Read moreRead less