线粒体DNA突变合并肾脏损害

Mitochondrial DNA mutation and renal involvement

目的:探讨3例线粒体病合并慢性肾脏病(CKD)患者的临床特点及预后。方法:2011年5月至2012年9月在南京军区南京总医院全军肾脏病研究所住院的CKD患者中共3例经线粒体DNA(mtDNA)基因检测确诊线粒体病,分析其肾外受累及肾脏损害的临床表现和肾活检病理特点,并观察其预后。结果:(1)3例患者中2例青少年(14岁),另1例30岁,全部患者均消瘦(体质量指数13～17kg/m2)。例1生长发育迟缓,例3为早产儿。例1、例2有糖尿病家族史,例2有尿毒症家族史。(2)3例患者病程3～7月,临床均表现为水肿、蛋白尿和胱抑素C增高,肾小管损伤明显,均无高血压和镜下血尿。例1和例3组织学示局灶节段性肾小球硬化(FSGS),例2肾小球轻度系膜增生伴小动脉节段透明变性。(3)3例患者中糖尿病(2例)、高乳酸血症(2例)、听力消失或下降(3例)、癫痫发作(1例)、脑梗塞(1例)、智力障碍(2例)、视野缺失(1例),心律失常(1例)。(4)3例患者均经基因测序并证实mtDNA3243A>G突变位点,例2母亲和弟弟也检出与患者相同突变位点。(5)经治疗3例均停免疫抑制剂,补充辅酶Q10和左卡尼汀等治疗,蛋白尿部分缓解,血清肌酐稳定。结论:本文首次在国内报道3例伴肾脏损害的线粒体病患者,提示这类患者并非罕见,临床除肾脏受累外均伴明显的心脏和中枢神经系统损害。临床医师应加强对此类疾病的认识。

Objective：Mitochondrial cytopathy is a heterogeneous disease with multiple organ system involvement. We report 3 mitochondrial eytopathy patients with mitochondrial DNA （mtDNA） point mutation and renal involvement. Methodology：Clinical feature and family history were collected. Renal biopsy was performed. DNA was isolated from peripheral blood leukoeytes of the patients. Polymerase chain reaction was performed to amplify the mtDNA. Sequencing analysis was used to detect the presence of any point mutation of mtDNA. Results： （ 1 ） General condition ： Two male and 1 female patients were involved,including 2 .adolescents（ 14 years old） and 1 adult（ 30 year old） ,with a BMI of 13 - 17 kg/m2. Case 1 had growth retardation and dysgnosia , case 3 was immature infant. Two cases had the family history of diabetes and case 2 had the family history of uremia. （ 2 ） Renal involvement ： all the patients had edema, proteinuria, and increased serum cystatin C levels. None of them was hypertensive. Urine test revealed severe tubular function injury without hematuria. Renal biopsy proved FSGS in cases 1 and case 3, mesengieal proliferation and arteriolar hyalinosis in case 2. （ 3 ） Systemic involvements including diabetes （ 2 cases ）, hyperlactacidemia （ 2 cases ）, auditory dysfunction （ 3 cases ）, epilepsy （ 1 cases） ,cerebral atrophy and ischemia（ 1 cases） ,dysnoesia（2 cases） ,visual field absence（ 1 case） ; muscular atrophy and weakness（2 cases）; arrhythmia（ 1 cases）. （4） Gene diagnosis：sequencing analysis proved presence of point mutation of mtDNA 3243 A 〉 G. （5） Treatment and prognosis ： All of them were not sensitive to steroid therapy , they were treated with coenzymeQ10 and levoearnitine. They have got a partial remission of proteinuria and stable serum creatinine. Conclusion： To our known, this is the first report of mtDNA 3243 A 〉 G point mutation and renal involvement in China. Early genediagnosis is essential to avoid misdiagnosis and mistreatment in patients suspicious of this disease.