儿童原发性1型高草酸尿症1例并文献复习

目的 总结儿童原发性1型高草酸尿症 (PH 1)临床资料，提高对该病的认识。方法 采集1例PH 1患儿的临床特点、影像学表现，肾结石分析信息；进行家系调查；对该家系相关成员进行AGXT基因外显子及附近调控区域直接测序，分析突变位点；文献综述。结果 女童，3岁时起病，首发症状为肉眼血尿，继腰、背部疼痛，体外震波碎石、排石治疗后结石复发，7年内进展为终末期肾病。腹部B超、X线平片和CT均提示多发双肾脏和输尿管结石。肾结石成份为单水草酸钙。未发现患儿家族有相同疾病的患者。AGXT基因分析发现，患儿存在c.242C>A（p.Ser81X）和c.823_824dupAG（p.Ser275delinsArgAlafs）杂合突变，其父亲携带c.823_824dupAG杂合突变，其母亲携带c.242C>A杂合突变。患儿为AGXT基因复合杂合突变，其中c.242C>A无义突变为首次报道。结论 PH 1为罕见遗传性疾病。经影像学证实为多发和复发性双肾结石，排除其他原因所致，应该考虑原发性高草酸尿症，肾结石成份和AGXT基因分析是PH 1诊断的重要手段，尤其AGXT基因分析在某些情况下可以替代肝穿刺成为PH 1确诊的无创检查；PH 1早期诊断和干预将会延缓肾功能恶化，改善预后。

Primary hyperoxaluria type 1 in one child and literature review

Objective To summarize and review the clinical data of a child with primary hyperoxaluria type 1 so as to improve its knowledge . Methods Clinical data of the case with PH 1were summarized, including clinical manifestations, imaging features and family investigation. AGXT gene analysis was performed in his family. Mutations of AGXT gene were scanned in normal control and related literatures were reviewed also. Results The age at onset was 3 years old. The first symptom was gross hematuria and followed by pain in back. He was diagnosed as urolithiasis. Urolithiasis recurred after removal of intraluminal stones by shock wave and endoscope. The patient was quickly progressed to end-stage renal disease within 7years. Multiple stones were found in kidney and ureter by ultrasonography, X-ray and computed tomography scan. Calcium oxalate monohydrate was confirmed by ingredient analysis of stone. No additional patient was identified in the family. c.242C>A and c.823_824dupAG heterozygous mutations in AGXT gene were detected in patient. AGXT gene analysis showed his father and mother had c.823_824dupAG and c.242C>A heterozygous mutations, respectively. c.242C>A heterozygous mutations is novel. These two mutations were not found in control subjects. Conclusion PH 1is a rare autosomal recessive disease. The disease should be considered when the patient had multiple and recurrent urolithiasis. Analysis of stone ingredient and AGXT gene is very useful for diagnosis. AGXT gene analysis is becoming first-choice method for diagnosis because it is noninvasive. Early diagnosis and management help to improve the outcome. The novel c.242C>A in our study extends the spectrum of AGXT gene mutations.