CHARACTERIZATION OF BIOTINIDASE DEFICIENCY

生物素酶是一种酶，它将生物素从终产物中切割出来， 生物素依赖的蛋白水解降解产物 羧化酶，从而回收维生素。 生物素酶活性为 大多数迟发性多发性羧化酶缺乏的儿童 缺陷 受影响的个体可能表现出神经系统和 皮肤特征，包括癫痫发作、张力减退、共济失调、皮肤 皮疹、脱发和发育迟缓，可能会发展为 最终死亡。 所有使用生物素酶的儿童 已经用生物素治疗的缺乏症患者的情况有所改善 临床上 由于该疾病符合入选的主要标准， 在新生儿筛查项目中，我们开发了一种简单的测试方法， 使用相同的血液浸泡的 大多数程序中使用的滤纸样本。 我们一直 筛查了自2009年以来在弗吉尼亚州出生的所有新生儿， 1984年1月24日，检测到三名新生儿患有 缺乏症和其中一名婴儿的两个受影响的兄弟姐妹。 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 新生儿缺乏酶。 我们建议 与目前在美国的指定医生合作 筛查生物素酶缺乏症， 确定有症状的个体以获得缺陷， 已识别出有症状个体的医生， 更好地了解原始特征和自然历史 精神紊乱的症状 将进行临床和生化评价， 定期对婴儿和儿童进行 通过新生儿筛查检测到生物素酶缺乏症或 在出现症状后被发现。 评价其 家庭成员，特别是兄弟姐妹，应该提供洞察力， 疾病表达的变化和可能的 存在良性变异。 此外，这项工作将提供 关于杂合子可能表现的信息 对于疾病和生物素的潜在副作用 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.