BACKGROUND Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay. METHODS Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (rs). RESULTS The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (rs = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls. CONCLUSIONS High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.

中文翻译：

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腺嘌呤磷酸核糖转移酶缺乏症的患者，携带者和健康对照组的尿中2,8-二羟基腺嘌呤排泄。

背景技术腺嘌呤磷酸核糖基转移酶（APRT）缺乏症是罕见的腺嘌呤代谢常染色体隐性遗传疾病，会导致难溶性2,8-二羟基腺嘌呤（DHA）的尿排泄过多，从而导致肾结石和慢性肾脏疾病。这项研究的目的是使用最近开发的超高效液相色谱-串联质谱（UPLC-MS / MS）分析评估APRT缺乏，杂合子和健康对照患者的尿DHA排泄。方法参加APRT缺乏症登记处和稀有肾结石协会生物库（http://www.rarekidneystones.org/）并提供24小时和第一时间清晨尿液样本进行DHA测量的患者符合研究条件。杂合子和健康个体作为对照。使用Wilcoxon-Mann-Whitney检验比较两组之间的24小时尿DHA排泄。使用Spearman相关系数（rs）检查关联。结果24小时尿DHA排泄量的中位值（范围）为138（64-292）mg / 24 h，并且早晨清晨空腹样本中DHA与肌酐（DHA / Cr）的比率为13（4-37）未接受黄嘌呤氧化还原酶抑制剂治疗的APRT缺乏患者的mg / mmol。24小时DHA排泄与早晨清晨尿液样本中的DHA / Cr比值高度相关（rs = 0.84，p <.001）。在未经治疗的患者的所有尿液样本中均检测到DHA，但在杂合子和健康对照的任何尿液样本中均未检测到DHA。结论在APRT缺乏的患者中观察到高尿DHA排泄，而杂合子和健康对照者未检测到尿DHA。