Biotin dependency due to a defect in biotin transport
Biotin dependency due to a defect in biotin transport
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DOI：
10.1172/jci200213138
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发表时间：
2002-06-01
影响因子：
15.9
通讯作者：
Mock, DM
中科院分区：
文献类型：
--
作者：
Mardach, R;Zempleni, J;Mock, DM
我们描述了一名3岁的男孩，患有生物素依赖，不是由生物素酶、全羧酸酶合成酶或营养性生物素缺乏引起的。我们试图确定他对生物素依赖的机制。这个孩子在18个月大的时候患上了急性脑病。尿有机酸提示几种生物素依赖的羧基酶缺乏。补充生物素后，症状迅速改善。血清生物素酶活性和生物素酶基因序列正常。PBMC和培养的皮肤成纤维细胞生物素依赖的羧基酶活性正常，但生物素全羧酶合成酶缺乏症除外。尽管细胞外生物素充足，但生物素退出会导致反复出现的异常有机酸尿，表明细胞内生物素缺乏。儿童新鲜PBMC和EB病毒转化的PBMC对生物素的摄取率分别约为正常新鲜和转化对照细胞的10%。对于来自父母的新鲜和转化的PBMC，生物素摄取率与常染色体隐性遗传缺陷的杂合性一致。生物素分解增加的可能性被排除，补充生物素的伪影和生物素膜通透性的普遍缺陷也被排除。这些结果为生物素运输中的一种新的遗传缺陷提供了证据。这名儿童是已知的第一个患有这种缺陷的人，现在应该包括在已确定的生物素依赖原因中。
We describe a 3-year-old boy with biotin dependency not caused by biotinidase, holocarboxylase synthetase, or nutritional biotin deficiency. We sought to define the mechanism of his biotin dependency. The child became acutely encephalopathic at age 18 months. Urinary organic acids indicated deficiency of several biotin-dependent carboxylases. Symptoms improved rapidly following biotin supplementation. Serum biotinidase activity and Biotinidase gene sequence were normal. Activities of biotin-dependent carboxylases in PBMCs and cultured skin fibroblasts were normal, excluding biotin holocarboxylase synthetase deficiency. Despite extracellular biotin sufficiency, biotin withdrawal caused recurrent abnormal organic aciduria, indicating intracellular biotin deficiency. Biotin uptake rates into fresh PBMCs from the child and into his PBMCs transformed with Epstein Barr virus were about 10% of normal fresh and transformed control cells, respectively. For fresh and transformed PBMCs from his parents, biotin uptake rates were consistent with heterozygosity for an autosomal recessive genetic defect. Increased biotin breakdown was ruled out, as were artifacts of biotin supplementation and generalized defects in membrane permeability for biotin. These results provide evidence for a novel genetic defect in biotin transport. This child is the first known with this defect, which should now be included in the identified causes of biotin dependency.