Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Medizinische Klinik für Endokrinologie und Stoffwechselmedizin, Campus Virchow, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
Genes (Basel). 2023 Jul 7;14(7):1408. doi: 10.3390/genes14071408.
Riboflavin transporter 1 (RFVT1) deficiency is an ultrarare metabolic disorder due to autosomal dominant pathogenic variants in . The RFVT1 protein is mainly expressed in the placenta and intestine. To our knowledge, only five cases of RFVT1 deficiency from three families have been reported so far. While newborns and infants with variants mainly showed a multiple acyl-CoA dehydrogenase deficiency-like presentation, individuals identified in adulthood were usually clinically asymptomatic. We report two patients with novel heterozygous variants. Patient 1 presented at the age of 62 with mild hyperammonemia following gastroenteritis. An acylcarnitine analysis in dried blood spots was abnormal with a multiple acyl-CoA dehydrogenase deficiency-like pattern, and genetic analysis confirmed a heterozygous variant, c.68C > A, p. Ser23Tyr. Patient 2 presented with recurrent seizures and hypsarrhythmia at the age of 7 months. Metabolic investigations yielded unremarkable results. However, whole exome sequencing revealed a heterozygous start loss variant, c.3G > A, p. Met1Ile in These two cases expand the clinical spectrum of riboflavin transporter 1 deficiency and demonstrate that symptomatic presentation in adulthood is possible.
核黄素转运蛋白 1 （RFVT1）缺乏症是一种极为罕见的代谢疾病，由. 中的常染色体显性致病性变异引起。RFVT1 蛋白主要在胎盘和肠道中表达。据我们所知，迄今为止，仅从三个家族中报道了五例 RFVT1 缺乏症病例。虽然携带 变异的新生儿和婴儿主要表现为多种酰基辅酶 A 脱氢酶缺乏症样表现，但在成年期被识别的个体通常没有临床症状。我们报告了两例具有新型杂合 变异的患者。患者 1 在 62 岁时因肠胃炎后出现轻度高氨血症。干血斑中的酰基肉碱分析异常，呈多种酰基辅酶 A 脱氢酶缺乏症样模式，基因分析证实存在杂合性 变异，c.68C > A，p. Ser23Tyr。患者 2 在 7 个月大时出现反复癫痫发作和高度不规则脑波。代谢研究结果无明显异常。然而，外显子组测序显示存在杂合性起始缺失变异，c.3G > A，p. Met1Ile 在 这两个病例扩展了核黄素转运蛋白 1 缺乏症的临床谱，并表明成年期出现症状是可能的。
