The Fabry-DiPaCT study, Version 1.4

  • Research type

    Research Study

  • Full title

    IMPROVING IDENTIFICATION OF PATIENTS WITH UNDIAGNOSED FABRY DISEASE: DIGITAL PHENOTYPING AND DETAILED CASCADE SCREENING

  • IRAS ID

    304721

  • Contact name

    Tarekegn Hiwot

  • Contact email

    tarekegn.geberhiwot@uhb.nhs.uk

  • Sponsor organisation

    University Hospitals Birmingham NHS Foundation Trust

  • Duration of Study in the UK

    1 years, 11 months, 31 days

  • Research summary

    Fabry Disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutation of the GLA gene. Clinical manifestations include anhidrosis or hypohidrosis, acroparaesthesia, corneal opacities, angiokeratomas, sensorineural hearing loss, non-specific bowel disturbance, progressive proteinuric kidney disease, progressive hypertrophic cardiomyopathy and cerebrovascular events.
    The prevalence of FD was previously estimated to be 1 in 117,000. Recent large genetic screening programs of new-borns however, reported significantly higher prevalence of between 1 in 1,300 to 1 in 7,800 of FD in males, demonstrating that FD is more frequent than previously understood. University Hospitals Birmingham (UHB) NHS FT is a national centre for FD with a catchment population of approximately 12 million. At a conservative estimate, UHB should be responsible for the care of approximately 1500 subjects, but our current case load stands at 218, albeit gradually increasing. Most referrals are seen at a late stage of disease, with advanced cardiomyopathy and/or renal disease, highlighting the urgent need for improved screening and earlier detection. The diagnosis of FD is commonly delayed by an average of 14 years in males and 19 years in females, a delay that is also seen in other rare diseases. There are also previous studies that have attempted to screen high risk cohorts. Two large national studies in Europe screened patients on haemodialysis for end stage kidney disease using blood spot tests and diagnosed FD in around 3.5%. In addition, similar studies in patients with cryptogenic stroke and cardiomyopathy diagnosed FD in up to 4.9% and 3%, respectively. These patients are all identified late in the course of disease, when currently available disease-modifying therapy may no longer be effective.
    Our hypothesis is that we will increase the detection of undiagnosed FD and shift diagnosis to an earlier stage when therapy is likely to be more effective. We will do this firstly, by using a synergistic, two-pronged approach of deep digital screening of all hospital records, followed by expert note review of selected patients. And secondly, we will undertake an in-depth cascade screening of up to three generations of identified FD patients.

  • REC name

    West Midlands - Solihull Research Ethics Committee

  • REC reference

    24/WM/0094

  • Date of REC Opinion

    30 Sep 2025

  • REC opinion

    Further Information Favourable Opinion