Biotinidase deficiency (BTD) is characterized by a wide range of genetic variants. However, the correlation between these variants and the biochemical phenotypes of BTD is not well-established due to the diversity of the BTD gene, the variable nature of biotinidase, and difficulties in measuring enzyme activity. This study aims to identify BTD gene variants in newborns screened for biotinidase deficiency in Southeastern Anatolia and to examine the correlation between these variants and biochemical phenotypes. BTD variant analysis and biotinidase enzyme (BT) activity measurements were performed on 711 newborns. Enzyme activity was measured using the colorimetric method. Biochemical phenotyping was categorized into three groups based on mean residual enzyme activity: profound (≤ 10%), partial (10.1–30%), and normal (> 30.1%). The pathogenicity of BTD gene variants was determined using BTD databases. The biochemical phenotypes were distributed as follows: a) profound: n = 22 (3%), b) partial: n = 95 (13.3%), and c) normal: n = 594 (83.7%). The mean enzyme activities (%) for these groups were 8.79 ± 1.87, 22.67 ± 4.55, and 97.98 ± 17.45, respectively. The most common alleles and their frequencies were p.D444H (n = 526) (37%), p.R157H (n = 172) (12.1%), and p.C33Ffster*36 (n = 73) (9%). The pathogenicity of the variants was as follows: pathogenic: 481 (33.8%), likely pathogenic: 4 (0.2%), and variant of uncertain significance (VUS): 538 (37.8%). In this large cohort in Southeastern Anatolia, the most common alleles were p.D444H, p.R157H, and p.C33Ffster*36 in BTD variants. The results indicate a low concordance between the biochemical phenotype and genotype in newborns with BTD. This study highlights the inadequacy of predicting the biochemical phenotype based solely on variant pathogenicity in biotinidase deficiency during the neonatal period.

中文翻译：

---

安纳托利亚东南部生物素酶缺乏症新生儿的基因型生化表型分析

生物素酶缺乏症 (BTD) 的特点是存在多种遗传变异。然而，由于 BTD 基因的多样性、生物素酶的可变性以及测量酶活性的困难，这些变异与 BTD 生化表型之间的相关性尚未明确。本研究旨在鉴定安纳托利亚东南部筛查出生物素酶缺乏症的新生儿中的 BTD 基因变异，并检查这些变异与生化表型之间的相关性。对 711 名新生儿进行了 BTD 变异分析和生物素酶 (BT) 活性测量。使用比色法测量酶活性。根据平均残留酶活性将生化表型分为三组：深度（≤ 10%）、部分（10.1-30%）和正常（> 30.1%）。使用 BTD 数据库确定 BTD 基因变异的致病性。生化表型分布如下：a) 深度：n = 22 (3%)，b) 部分：n = 95 (13.3%)，c) 正常：n = 594 (83.7%)。这些组的平均酶活性 (%) 分别为 8.79 ± 1.87、22.67 ± 4.55 和 97.98 ± 17.45。最常见的等位基因及其频率是 p.D444H (n = 526) (37%)、p.R157H (n = 172) (12.1%) 和 p.C33Ffster*36 (n = 73) (9%)。变异的致病性如下：致病：481（33.8%），可能致病：4（0.2%），意义不确定的变异（VUS）：538（37.8%）。在安纳托利亚东南部的这个大队列中，最常见的等位基因是 BTD 变体中的 p.D444H、p.R157H 和 p.C33Ffster*36。结果表明 BTD 新生儿的生化表型和基因型之间的一致性较低。这项研究强调了仅根据新生儿期生物素酶缺乏症的变异致病性来预测生化表型的不足。