RESEARCH: Recruiting Patients and Healthy Controls for Newborn Screening Research Study

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 Climb 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 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.

Healthy controls: The researchers are also recruiting healthy controls at Sheffield Children’s NHS Foundation Trust and Birmingham Children’s Hospital NHS Foundation Trust. Healthy controls are those individuals that have not been diagnosed previously with NBS disorders namely PKU, MCADD, MSUD, IVA, GA1, HCU, Cystic Fibrosis (CF), Sickle Cell Disease (SCD) or Congenital Hypothyroidism (CHT). Each volunteer will be asked to provide a blood sample and a finger-prick blood spot sample from which DNA will be extracted and sequenced for specific disorder genes. This will help the team decide if it is possible to use newborn blood spot samples to screen for rare genetic disorders using NGS. After getting consent, the DNA will also be used as a control sample to develop a database for NBS disorders. Volunteers will be asked a few short questions about their medical history and ethnicity, so that the team can match healthy control and newborn ethnicities. All healthy control participants will receive a £10 shopping voucher and refreshments. All samples will be anonymised meaning that participant identities will only be known to the research nurse but not to the genetics laboratory.

Interested participants:

If you are interested in taking part or if you have any queries about the study, please contact the Project Manager Clare.Gladding@sch.nhs.uk.

Funding bodies:

This study was awarded Health Innovation Challenge Funding from the Department of Health and the Wellcome Trust. The collaborative research project officially started on 1st March 2015 and will end on 1st March 2018.