Database Development for Newborn Screening Disorders.
Research type
Research Study
Full title
A study to develop a genotype-phenotype correlative database for six Newborn Screening Disorders by performing Next Generation DNA Sequencing on a small panel of genes and collecting medical record information from screen positive and clinically affected patients
IRAS ID
178452
Contact name
Clare Gladding
Contact email
Sponsor organisation
Sheffield Children’s NHS Foundation Trust
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Newborn screening (NBS) identifies conditions that are difficult to detect clinically, yet benefit from early recognition and intervention. In the UK, newborn babies are currently screened for nine rare disorders using dried blood spots (DBS) taken shortly after birth. The screening tests use chemicals in the DBS to identify babies affected with these disorders. Some “screen positive” babies have genetic tests to confirm the disorder. The disorders being tested are potentially life-threatening but are treatable if identified early. The severity of disorders differs between patients and the link between genetic defects (mutations) and disorder severity are often not well understood.
The purpose of this project is to improve our understanding of how genetic mutations relate to patient symptoms and disease severity. We can then incorporate genetic testing into newborn screening programmes to help clinicians decide on what is the best treatment for patients. It would also help clinicians determine whether patients should or should not be treated who show biochemical abnormalities but may be clinically unaffected. We will use a new technology, Next Generation DNA Sequencing (NGS) to find mutations in six disorders screened in newborns: Phenylketonuria (PKU), Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD), Maple Syrup Urine Disease (MSUD), Isovaleric Acidaemia (IVA), Glutaric Aciduria Type 1 (GA1), Homocystinuria (pyridoxine unresponsive; HCU). We will collect details of patient symptoms, blood chemicals and genetic mutations in a database in order to understand how genetic changes are linked to disorder severity. This project will collect genetic sequencing data and medical record information from 130 screen positive patients and 130 clinically affected patients. Anonymised genetic data from 150 healthy controls (from an existing approved study) will also be used if the participant has consented. The database will help clinicians provide more appropriate and personalised treatment to affected babies, children and adults.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
16/WM/0145
Date of REC Opinion
5 Apr 2016
REC opinion
Further Information Favourable Opinion