Potter M, Hammond J W, Sim K G, Green A K, Wilcken B
New South Wales Biochemical Genetics Service, The Children's Hospital at Westmead, (Sydney), Australia.
J Inherit Metab Dis. 2001 Feb;24(1):5-14. doi: 10.1023/a:1005682017337.
The most direct test of functional capacity of the liver in nitrogen disposal is to stress the urea cycle with a high protein load. This has been used in the diagnosis of heterozygosity for ornithine carbamoyltransferase deficiency for many years by measuring the subsequent excretion of orotic acid in urine. Reports have shown some ambiguity in both this and the more recent allopurinol test. We investigated the effects of different foods as the protein load and of different analytical methods. A standardized protocol was developed, giving 35 g protein per m2 surface area as steamed fat-free chicken breast to be eaten within 30 min. Urine was collected at zero time and over 0-2, 2-4 and 4-6 h. Compliance was checked by assessing excretion of amino acids. Diagnostic sensitivity was improved by reference to the change in excretion, i.e. the ratio of excretions 2-4 h/0-2 h. Extension of the test to 6 h gave no diagnostic advantage over a 4 h test. Comparison of the analysis of total orotic acids by the photometric method of Harris and Oberholtzer, the reference method for this study, with that by the method of Goldstein and colleagues showed that the latter gave erratic results with some false positives. However, comparison of the method of Harris and Oberholtzer with specific orotic acid analysis by a modification of the stable-isotope internal standard method of Rimoldi and colleagues yielded the same diagnoses. The improved protein load test gave a clearly positive result in all 16 obligate heterozygotes and 2 possible heterozygotes tested from 14 kindred, and a clearly negative result in all 18 control subjects and all 6 of the possible heterozygotes who were later shown by DNA studies not to carry the family mutation. The test appears at least as sensitive and specific as the allopurinol test, and is more convenient because of the short period of sample collection.
在氮代谢方面，对肝脏功能能力最直接的测试是通过高蛋白负荷来刺激尿素循环。多年来，通过测量随后尿中乳清酸的排泄量，此方法已被用于鸟氨酸氨甲酰基转移酶缺乏症杂合子的诊断。报告显示，无论是这种方法还是最近的别嘌呤醇测试都存在一些不明确之处。我们研究了不同食物作为蛋白质负荷以及不同分析方法的影响。制定了一个标准化方案，每平方米体表面积给予35克蛋白质，以无脂蒸鸡胸肉的形式在30分钟内食用。在0时刻以及0 - 2小时、2 - 4小时和4 - 6小时收集尿液。通过评估氨基酸排泄量来检查依从性。通过参考排泄量的变化，即2 - 4小时排泄量与0 - 2小时排泄量的比值，提高了诊断敏感性。将测试延长至6小时相较于4小时测试并无诊断优势。将本研究的参考方法——哈里斯和奥伯霍尔泽的光度法对总乳清酸的分析，与戈尔茨坦及其同事的方法进行比较，结果显示后者得出的结果不稳定且有一些假阳性。然而，哈里斯和奥伯霍尔泽的方法与通过对里莫尔迪及其同事的稳定同位素内标法进行改进后的特定乳清酸分析方法进行比较，得出了相同的诊断结果。改进后的蛋白质负荷测试在来自14个家系的所有16名纯合子杂合子和2名可能的杂合子测试中均给出了明确的阳性结果，在所有18名对照受试者以及后来经DNA研究表明未携带家族突变的所有6名可能的杂合子中均给出了明确的阴性结果。该测试至少与别嘌呤醇测试一样敏感和特异，并且由于样本收集期短而更方便。
