CHARACTERIZATION OF BIOTINIDASE DEFICIENCY

生物素酶是将生物素从最终的 依赖生物素的蛋白质降解产物 羧基酶，从而循环利用维生素。生物素酶活性为 大多数晚发性多发性羧基酶儿童存在缺陷 失败性。受影响的个体可能会表现出神经性和 皮肤特征包括癫痫发作、低眼压、共济失调、皮肤 皮疹、脱发和发育迟缓，可能会进展到 来了，最终就死了。所有患有生物素酶的儿童 经生物素治疗的缺乏症患者已有所改善 从临床上看。因为这一障碍符合纳入的主要标准 在新生儿筛查项目中，我们开发了一种简单的测试 用同样的血液浸泡法测定生物素酶活性 大多数程序中使用的滤纸样本。我们一直在 之后对弗吉尼亚州出生的所有新生儿进行筛查 1984年1月24日，并发现三名新生儿患有 其中一名婴儿患有缺乏症和两名受影响的兄弟姐妹。 根据我们的结果，十几个州和十个外国 各国已经开始或将开始类似的新生儿筛查 程序。其中几个程序已经检测到 患有酶缺乏症的新生儿。我们提议 与各州的指定医生合作，目前 生物素酶缺乏症的筛查和患有 确定有症状的人以获得缺陷和 已确定有症状的个人的医生将获得 对原始地貌和自然历史有更好的了解 失调症的症状。临床和生化评估将 定期对婴幼儿和儿童进行检查 新生儿筛查发现的生物素酶缺乏症或有 在出现症状后被确认。对他们的评估 家庭成员，特别是兄弟姐妹，应该提供对 精神障碍的表达变异及其可能 良性变异的存在。此外，这项工作将提供 关于杂合子可能表现的信息 治疗这种疾病和生物素的潜在不良反应 治疗。

Biotinidase is the enzyme that cleaves biotin from the final products of the proteolytic degradation of biotin-dependent carboxylases, thus recycling the vitamin. Biotinidase activity is deficient in most children with late-onset multiple carboxylase defeiciency. Affected individuals may exhibit neurologic and cutaneous features including seizures, hypotonia, ataxia, skin rash, alopecia and developmental delay, which may progress to come and ultimately death. All children with biotinidase deficiency who have been treated with biotin have improved clinically. Since the disorder met the major criteria for inclusion in newborn screening programs, we developed a simple test for determining biotinidase activity using the same blood-soaked filter paper samples used in most programs. We have been screening all the newborn infants born in Virginia since January 24, 1984 and have detected three newborns with the deficiency and two affected siblings of one of these infants. Based on our results more than a dozen states and ten foreign countries have started or will start similar newborn screening programs. Several of these programs have already detected newborns with the enzyme deficiency. We proposed to collaborate with designated physicians in states that are currently screening for biotinidase deficiency and physicians who have identified symptomatic individuals to obtain a deficiency and physicians who have identified symptomatic individuals to obtain a better understanding of the initial features and natural history of the disorder. Clinical and biochemical evaluations will be performed at regular intervals on infants and children with biotinidase deficiency detected by newborn screening or who have been identified after developing symptoms. Evaluation of their family members, particularly siblings, should provide insight into the variation of expression of the disorder and the possible existence of benign variants. Moreover, this work will provide information about the possible manifestations in heterozygotes for the disorder and the potential adverse effects of biotin treatment.