Department of Child Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Orphanet J Rare Dis. 2024 Nov 1;19(1):410. doi: 10.1186/s13023-024-03428-y.
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.
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.
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.
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.
核黄素转运蛋白缺陷症（RTD）是一种核黄素转运的先天性错误，如果不进行治疗，会导致进行性神经症状。虽然有症状的 RTD 婴儿会迅速恶化，但在儿童期或成年期的表现则更为缓慢。其症状与更常见的疾病重叠，存在误诊的风险，而且由于 2010 年才发现 RTD 的遗传基础，因此很可能以前的患者没有接受过检测。口服核黄素（维生素 B2）治疗可以阻止疾病进展，甚至可以挽救生命。我们假设在出现症状时可能未被识别，因此我们进行了一项数据挖掘研究，以在一家三级转诊医院中发现未确诊的 RTD 患者。
通过医疗数据文本挖掘工具，对 2004 年 1 月至 2021 年 7 月期间在阿姆斯特丹大学医学中心就诊的所有患者的电子健康记录（EHR）进行系统搜索。筛选出与听力损失或听觉神经病谱系障碍以及关键临床症状或核黄素相结合的预定义搜索词相匹配的匿名化患者记录，如果未发现可能表明 RTD 的症状的明确替代诊断，则将其纳入研究。纳入的患者被提供了基因检测。我们记录了可能患有 RTD 的患者总数、接受 RTD 基因检测的患者数量以及基因检测的结果。
自动筛查了 2288901 名患者的 EHR。发现 13 名可能患有 RTD 的患者，并为他们提供了基因检测。其中 7 名患者选择不参与。对 6 名患者进行了基因检测，但结果均为阴性。数据挖掘确实在医院中发现了所有先前已知的 RTD 患者。
通过对三级转诊医院中所有年龄段的大样本患者进行筛查，在 17 年的时间跨度内未发现新的 RTD 患者。尽管并非所有疑似患者都接受了基因检测，但我们的研究结果表明 RTD 的患病率较低，在三级转诊医院中漏诊的可能性有限。
