Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study.

Background: Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital.

Methods: A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing.

Results: EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital.

Conclusions: By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.