Diagnosing rare inherited metabolic diseases using exome sequencing
Research type
Research Study
Full title
An evaluation of the use of exome next generation sequencing to determine in the diagnosis of local children with rare, undiagnosed inherited metabolic diseases.
IRAS ID
186711
Contact name
Richard J Kirk
Contact email
Sponsor organisation
Sheffield Childrens NHS Foundation Trust
Duration of Study in the UK
1 years, 5 months, 30 days
Research summary
Inherited metabolic diseases are a large group of individually rare, but collectively common, conditions that affect the way the body takes up, stores and uses energy. They usually occur in infancy or childhood and can be very severe or even fatal. Treatments include specific medications or special diets. Diagnosis is currently made using clinical assessment, biochemical and genetic testing. However, some individuals cannot be given a diagnosis, meaning that treatment may not be optimal, and that they may have many hospital appointments and further tests before any diagnosis is made.
Next generation sequencing has revolutionised genetic testing in the NHS, allowing many genes to be sequenced at the same time and for a reasonable price compared to previous methods. An advanced form of this - exome sequencing – is able to look at all known protein-coding genes.
In this study, we will harness the power of exome sequencing to look at ten children without a diagnosis who attend the metabolic clinic at Sheffield Children’s Hospital. We will sequence the exomes of these children, then use the available clinical and biochemical information to focus our analysis, with the aim of giving a definitive diagnosis.
Sheffield Children’s Hospital has the expertise needed to carry this out: metabolic doctors experienced in diagnosing these conditions; clinical scientists with years of experience in interpreting biochemical and genetic results; three next generation sequencing machines; and a bioinformatician skilled in processing the huge amounts of genetic data produced.
We expect to show that this technology, together with good clinical and biochemical assessment, will diagnose more patients with these diseases, and reduce delayed diagnosis. We will then apply for funding for a national study to gain approval for this method to be used as standard across the NHS.
REC name
South East Scotland REC 01
REC reference
15/SS/0206
Date of REC Opinion
11 Dec 2015
REC opinion
Further Information Favourable Opinion