The allopurinol load test lacks specificity for primary urea cycle defects but may indicate unrecognized mitochondrial disease
The allopurinol load test lacks specificity for primary urea cycle defects but may indicate unrecognized mitochondrial disease
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DOI：
10.1023/a:1005406205548
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发表时间：
1999-04-01
影响因子：
4.2
通讯作者：
Fairbanks, LD
中科院分区：
文献类型：
--
作者：
Bonham, JR;Guthrie, P;Fairbanks, LD
选择33名年龄在2周到12岁之间的儿童进行别嘌呤醇负荷，其中16名基于常规有机酸分析检测到的尿乳清酸排泄增加（A组），17名基于提示尿素循环缺陷的临床原因（B组）。A组16例患者中有13例别嘌呤醇负荷试验阳性，平均乳清酸峰值为64.0 μ mol/mmol肌酐（参考范围上限，13.2），B组17例患者中有11例别嘌呤醇负荷试验阳性，平均乳清酸峰值为41.0 μ mol/mmol肌酐（参考范围上限，13.2）。对这些患者进行了彻底的调查，包括尿液和血浆氨基酸分析，在17例病例中进行了肝活检组织学检查，并测量了鸟氨酸氨甲酰转移酶（OCT）和氨甲酰磷酸合成酶（CPS）活性，但未能确定尿素循环障碍的任何证据。然而，在11例患者中进行的肌肉活检显示了4例线粒体疾病的证据，其中2例是基于呼吸链酶活性降低，2例是基于mtDNA异常。这些结果表明，增加乳清酸排泄在患病儿童可能并不罕见，积极别嘌呤醇负荷试验结果可能并不表明一个特定的遗传性尿素循环缺陷。此外，这些结果提出了一个有趣的可能性，即尿素生成缺陷可能是某些个体线粒体疾病的一个特征。
Thirty-three children ranging from 2 weeks to 12 years of age were selected for allopurinol loading, 16 on the basis of an increased urinary orotate excretion detected by routine organic acid analysis (group A) and 17 for clinical reasons suggesting a urea cycle defect (group B). The allopurinol load test proved positive in 13 of 16 patients from group A, mean peak orotate 64.0 mu mol/mmol creatinine (upper limit of reference range, 13.2) and 11 of 17 patients from group B, mean peak orotate 41.0 mu mol/mmol creatinine (upper limit of reference range, 13.2). Thorough investigation of these patients including urinary and plasma amino acid analysis and, in 17 cases, liver biopsy for histology and measurement of ornithine carbamyltransferase (OCT) and carbamyl-phosphate synthetase (CPS) activity failed to identify any evidence of a urea cycle disorder. However, muscle biopsies performed in 11 patients showed some evidence of mitochondrial disease in four cases, two defined on the basis of reduced respiratory chain enzyme activity and two on the basis of mtDNA abnormalities. These findings indicate that an increased excretion of orotate in sick children may not be uncommon and that a positive allopurinol load test result may not indicate a specific inherited urea cycle defect. In addition, these results raise the interesting possibility that defective ureagenesis may be a feature of mitochondrial disease in some individuals.