Research Study for Existing Newborn Screening Conditions

At Sheffield Children’s NHS Foundation Trust, Dr Ann Dalton and Professor Anne Goodeve are leading an exciting research project to investigate the Applications of Next Generation DNA Sequencing (NGS) in Newborn Screening (NBS). This study is being supported by Metabolic Support UK to ensure that patient and public opinion is being considered throughout the course of the research project.

Why is this research being performed?
NBS programmes are used worldwide to identify babies affected with rare, often fatal, but treatable disorders. Analysis of dried blood spot (DBS) samples taken shortly after birth provides cost-effective testing in a short time frame. Infants found to have a specific condition will receive rapid medical attention, but predicting disease severity and appropriate management in a child without symptoms can be challenging.

The research team will use NGS to analyse genetic changes associated with NBS disorders. NGS is a relatively new technique that enables many genes to be analysed at the same time, rather than individually as was previously done. For the first aim, clinical details including patient symptoms, blood chemicals and genetic mutations will be entered into a secure database. Understanding better the relationship between the genetics and the clinical symptoms in these diseases, will help provide improved and personalised treatment to affected babies, children and adults. For the second aim, healthy control samples will be used to optimise DNA extraction from DBS samples for NGS genetic analysis. The DNA extraction and NGS method will be developed and cost-estimated such that it is high-throughput, efficient and automated for multiple DBS samples tested in NBS. This project will establish whether NGS can be used as a follow-up test for NBS to provide valuable additional information alongside existing UK NBS programmes or perhaps even as an initial test in the future.

Who would the researchers like to recruit?
Patients: The research team is currently seeking children and adult patients from Sheffield Children’s NHS Foundation Trust and other Trusts including Birmingham Children’s Hospital, Central Manchester University Hospitals, Great Ormond Street Hospital for Children and Guy’s and St Thomas’ with the following Newborn Screening (NBS) disorders:

  • 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)

At the patient’s hospital, participants will be asked to provide a blood sample. DNA from this sample will be used for genetic sequencing of specific genes associated with these inherited disorders. Participants will need to consent to sharing of medical record information such as symptoms, treatments and test results including genetics. All information collected will be stored securely in a confidential project database. Hospital visits with the research nurse should last approximately thirty minutes and refreshments will be provided. It is recommended that children are accompanied by a parent, carer or relative during the hospital visit. Participants may withdraw from the study at any point.

Interested participants:
If you are interested in taking part or if you have any queries about the study, please contact the Project Manager on

Funding bodies:
This research is supported by an award from the Health Innovation Challenge Fund (HICF-R9-518), a parallel funding partnership between the Department of Health and the Wellcome Trust. The collaborative research project officially started on 1st March 2015 and will end in August 2019.