生物素酶(BTD)是回收生物素所必需的,一种水溶性复合维生素B,是参与脂肪酸合成的四种羧化酶的辅酶,氨基酸分解代谢和糖异生。如果未经治疗,全部或部分BTD缺陷导致常染色体隐性遗传性有机酸尿症,其临床特征,主要表现在生命的最初几年,包括,癫痫发作,皮疹,和脱发。根据残留的BTD酶活性,可以鉴定部分或全部的生物素酶缺陷。全球范围内严重和部分生物素酶缺乏症的发生率估计约为60.000中的1。我们报告了在466.182名新生儿中进行生物素酶缺乏症新生儿筛查的十二年经验。当出现阳性筛查结果时,我们对患者进行了临床评估,并向家属提供了遗传咨询.在所有召回的新生儿中进行了BTD基因的分子分析。新生儿筛查可识别出75例BTD缺陷,发生率约为1:6.300。比全球报告的发病率高10倍。在所有患者的基因组水平上证实了BTD缺乏,表明p.(Asp444His)氨基酸取代和复杂等位基因p.(Ala171Thr)/p.(Asp444His)在分析的意大利新生儿中。四个新的突变(两个小的缺失,一个终止突变和一个错义突变)和一个新的组合等位基因改变被鉴定。我们的数据表明,在意大利人群中,生物素酶缺陷的发生率很高,很可能是由于某些突变的频率很高。
The biotinidase (BTD) enzyme is essential for recycling biotin, a water-soluble B-complex vitamin that is the coenzyme of four carboxylases involved in fatty acid synthesis, amino acid catabolism and gluconeogenesis. If untreated, total or partial BTD deficiencies lead to an autosomal recessive inherited organic aciduria whose clinical features, mainly presenting in the first years of life, include, seizures, skin rash, and alopecia. Based on residual BTD enzyme activity it is possible to identify partial or total biotinidase deficiency. The incidence of profound and partial biotinidase deficiency worldwide is estimated to be about 1 in 60.000. We report twelve years of experience in the newborn screening of biotinidase deficiency on 466.182 neonates. When a positive screening result occurred, a clinical evaluation was made of the patient and genetic counselling was offered to the family. Molecular analysis the BTD gene was carried out in all recalled neonates. Newborn screening lead to the identification of 75 BTD deficiencies with an incidence of about 1:6.300 births, ten times higher than the reported worldwide incidence. BTD deficiency was confirmed at a genomic level in all patients, demonstrating a high frequency of the p.(Asp444His) amino acid substitution and the complex allele p.(Ala171Thr)/p.(Asp444His) in the analyzed Italian newborns. Four new mutations (two small deletions, one stop mutation and one missense mutation) and a new combined allelic alteration were identified. Our data suggests that there is a high incidence of the biotinidase defect in the Italian population, most likely due to the high frequency of certain mutations.