Suormala T, Wick H, Bonjour J P, Baumgartner E R
Eur J Pediatr. 1985 May;144(1):21-6. doi: 10.1007/BF00491919.
We have investigated four patients from three unrelated families with typical clinical and biochemical features of "late-onset" multiple carboxylase deficiency. All patients suffered from biotinidase deficiency (plasma biotinidase activities 1.4%-3% of normal). Intestinal absorption of biotin, measured in three of the patients using a single load of 1.5 micrograms/kg, was found to be normal. Deficient activities of the mitochondrial biotin-dependent carboxylases in lymphocytes of one of these patients increased from 25% of mean basal control values to 33%-36% within 45 min and to 46%-47% within 2 h of the 1.5 micrograms/kg biotin load. After a high biotin load of 100 micrograms/kg, the values normalised within 45 min in all three patients studied. These results indicate normal cellular transport of biotin and normal holocarboxylase synthesis. After cessation of biotin supplementation, the plasma and urinary biotin in patients decreased to subnormal levels. In one patient, available for more detailed studies, both plasma and urinary biotin declined about twice as fast as in controls (apparent half-life 12-14 h in the patient and 26 h in controls). These results point to increased excretion of free biotin in our patient. Renal loss of biotin is one of the factors contributing to the high biotin requirement observed in patients with biotinidase deficiency.
我们研究了来自三个无亲缘关系家庭的四名患者，他们具有“迟发性”多种羧化酶缺乏症的典型临床和生化特征。所有患者均患有生物素酶缺乏症（血浆生物素酶活性为正常水平的1.4%-3%）。通过给三名患者单次负荷1.5微克/千克来测量生物素的肠道吸收情况，发现其正常。其中一名患者淋巴细胞中线粒体生物素依赖性羧化酶的活性在给予1.5微克/千克生物素负荷后45分钟内从平均基础对照值的25%增加到33%-36%，2小时内增加到46%-47%。在给予100微克/千克的高生物素负荷后，所有三名接受研究的患者的值在45分钟内恢复正常。这些结果表明生物素的细胞转运正常且全羧化酶合成正常。停止补充生物素后，患者血浆和尿液中的生物素水平降至低于正常水平。在一名可供进行更详细研究的患者中，血浆和尿液中的生物素下降速度约为对照组的两倍（患者的表观半衰期为12-14小时，对照组为26小时）。这些结果表明我们的患者中游离生物素的排泄增加。生物素的肾脏丢失是导致生物素酶缺乏症患者生物素需求量高的因素之一。
