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.

生物素酶（BTD）酶对于循环利用生物素是必不可少的。生物素是一种水溶性B-复合维生素，是参与脂肪酸合成，氨基酸分解代谢和糖异生的四种羧化酶的辅酶。如果不进行治疗，则BTD的全部或部分缺陷会导致常染色体隐性遗传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。基于残留的BTD酶活性，可以确定部分或全部生物素酶缺乏症。据估计，全世界范围内严重和部分生物素酶缺乏症的发生率约为60.000分之一。

我们报告了对466.182例新生儿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，将对该患者进行临床评估，并向该家庭提供遗传咨询。BTD基因的分子分析在所有召回的新生儿中进行。

新生儿筛查可鉴定出75种BTD缺陷，出生率约为1：6.300，比所报道的全球发病率高十倍。在所有患者中均在基因组水平上证实了BTD缺乏，这表明在分析的意大利新生儿中p。（Asp444His）氨基酸取代和复合等位基因p。（Ala171Thr）/ p。（Asp444His）的频率很高。确定了四个新突变（两个小缺失，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。

我们的数据表明，意大利人群中生物素酶缺陷的发生率很高，这很可能是某些突变的发生频率很高。