Prevalence and Data-Driven Exploration of Pre-Diagnostic Symptoms and Features of Gilbert's Syndrome in the UK Primary Care Population.

Background: Gilbert's syndrome (GS) is a common genetic disorder marked by elevated bilirubin levels due to UGT1A1 enzyme deficiency. While jaundice and some adverse drug reactions are the primary recognised clinical features, individuals with GS frequently report non-specific symptoms like fatigue, brain fog, and abdominal pain. This study investigates the symptoms and diagnostic triggers of GS using UK primary care electronic health records.

Methods: We analysed data from the IQVIA Medical Research Database, covering over 11 million active UK patients. Individuals with a recorded GS diagnosis were identified and their sociodemographic profiles described. Using a nested case-control design, we applied machine learning-based feature selection to pinpoint key clinical features recorded up to five years before diagnosis. These features were then examined longitudinally by sex to distinguish persistent symptoms from short-term diagnostic triggers.

Results: The estimated UK prevalence of GS was 180.4 per 100,000 (95% CI: 174.4-186.6), with diagnoses more common in men, peaking around age 35, and more frequent in areas of least social deprivation. Among 9,240 GS cases and 150,846 controls, machine learning identified key diagnostic themes including jaundice, abnormal liver function tests, abdominal pain, fatigue, bowel changes, and sleep disturbances. While most of these features appeared primarily in the year prior to diagnosis, only abdominal pain and fatigue were consistently more common in GS cases up to five years before diagnosis.

Conclusion: Our findings highlight both expected and novel GS diagnostic triggers. While many features likely reflect known symptomology or incidental detection via routine testing, the persistent presence of fatigue and abdominal pain suggests they may be under-recognised symptoms of GS. These findings warrant further investigation, and the data-driven approach used here may help uncover early signs of other underdiagnosed genetic conditions.