Abstract：
Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in APRT (OMIM #102600). APRT deficiency results in increased urinary excretion of 2,8-dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11-year-old brother and his 14-year-old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in APRT with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere-like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister\'s diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the APRT gene in a pair of siblings with greater phenotypic severity in the male.
摘要：
腺嘌呤磷酸核糖转移酶（APRT）缺乏症是一种常染色体隐性遗传疾病，是由于APRT（OMIM＃102600）突变引起的尿石症的罕见原因。APRT缺乏导致2,8-二羟基腺嘌呤（DHA）的尿排泄增加，可引起尿石症和肾衰竭。然而,及时诊断，APRT缺乏症患者可接受黄嘌呤氧化还原酶抑制剂治疗,该抑制剂可减少尿DHA排泄并改善预后.我们报道了一对兄弟姐妹，一个11岁的兄弟和他14岁的妹妹，具有复合杂合变体c.270del（第Lys91Serfs*46）和c.484_486del（p。Leu162del）在APRT中具有不同的APRT缺乏临床表现。兄弟在17个月大时出现尿石症和严重的急性肾损伤。他的姐姐身体健康，无症状，肾功能正常，没有发生肾结石。姐妹在筛查时的尿液显微镜上报告了带有同心和径向标记的棕色圆盘或球形晶体。进一步的实验室证据证实了姐妹的诊断，即缺乏红细胞裂解物APRT活性，尿DHA水平相应升高。总之,我们在男性表型严重程度更大的一对兄弟姐妹中发现了APRT基因的新突变.
