CAJ | 학술논문

目的探讨Fabry病肾损害的临床病理及α-半乳糖苷酶A(α-Gal A)基因(GLA 基因)突变的特点.方法回顾性分析14例Fabry病患者的临床、肾脏病理及GLA基因突变等特点.结果 Fabry病肾损害在肾活检患者中检出率为0.074％,平均确诊年龄(30.57±9.32)岁,男∶女=2.5∶1.尿蛋白量中位数为1.71 g/24 h[(0.32～ 4.71)g/24 h].5例有血尿,4例有肾功能受损,肾外受累的表现以血管角质瘤最多见(10/14),其次为心脏病变(6/14).经典型患者9例,迟发型5例,其中6例有肾脏病家族史.肾脏病理光镜下可见明显的肾小球细胞空泡变性,部分患者可见硬化的肾小球.电镜下2例女性患者为部分足细胞内有髓磷脂样小体形成,其余病例所有足细胞内均可见髓磷脂样小体.4例测定α-Gal A活性的先证者均低于正常值.12例先证者进行了GLA基因突变分析,11例发现有GLA基因突变.3个新突变为碱基插入或缺失突变,临床表型均为经典型Fabry病.大多数迟发型患者携带的基因突变位于酶结构的包埋区或部分包埋区(3/11).在已证实的GLA基因突变中,携带I91T、R112H、Q312H的先证者主要表现为“迟发型”；携带W162X、F169S、S201F、N272K及L310R的先证者均表现为“经典型”.结论本组Fabry病肾损害患者占肾活检的0.074％,常伴有血管角质瘤及心脏受累,且不同的GLA基因突变可能与患者的表型密切相关.
목적 탐토Fabry병신손해적림상병리급α-반유당감매A(α-Gal A)기인(GLA 기인)돌변적특점.방법 회고성분석14례Fabry병환자적림상、신장병리급GLA기인돌변등특점.결과 Fabry병신손해재신활검환자중검출솔위0.074％,평균학진년령(30.57±9.32)세,남∶녀=2.5∶1.뇨단백량중위수위1.71 g/24 h[(0.32～ 4.71)g/24 h].5례유혈뇨,4례유신공능수손,신외수루적표현이혈관각질류최다견(10/14),기차위심장병변(6/14).경전형환자9례,지발형5례,기중6례유신장병가족사.신장병리광경하가견명현적신소구세포공포변성,부분환자가견경화적신소구.전경하2례녀성환자위부분족세포내유수린지양소체형성,기여병례소유족세포내균가견수린지양소체.4례측정α-Gal A활성적선증자균저우정상치.12례선증자진행료GLA기인돌변분석,11례발현유GLA기인돌변.3개신돌변위감기삽입혹결실돌변,림상표형균위경전형Fabry병.대다수지발형환자휴대적기인돌변위우매결구적포매구혹부분포매구(3/11).재이증실적GLA기인돌변중,휴대I91T、R112H、Q312H적선증자주요표현위“지발형”；휴대W162X、F169S、S201F、N272K급L310R적선증자균표현위“경전형”.결론 본조Fabry병신손해환자점신활검적0.074％,상반유혈관각질류급심장수루,차불동적GLA기인돌변가능여환자적표형밀절상관.
Objective To elucidate the clinicopathological and hereditary characteristics in Fabry nephropathy.Methods The clinical and pathological features of 14 patients with Fabry nephropathy were collected.The activities of α-Gal A were measured in 4 probands.Screenings of GLA mutations were done in 12 patients.Results The ratio of Fabry nephropathy in the patients with renal biopsy was 0.074 ％ (14/19 005),the average diagnostic age was (30.57±9.32) years,male to female ratio was 2.5∶ 1.All the patients had proteinuria,and the median of urine total protein (UTP)was 1.71 g/24 h (0.32-4.71 g/24 h).Two of them got nephrotic proteinuria,5 of them got microscopic hematuria,4 of them got renal function insufficiency.Angiokeratomas was the most common manifestation (10/14),followed by cardiac involvement (6/14).Hypohidrosis and diseases of central neural system could also be seen in these patients.There were 9 classic phenotype,the remaining 5 were variants/renal variants.The family information was collected in 10 pedigrees,6 of them had family histories of kidney disease.Renal pathology showed vacuolization of glomerular visceral epithelial cells was the prominent feature,global and segmental glomerulosclerosis were seen in some patients by light microscopy.The myelin bodies or zebra bodies were identified in podocytes by electron microscopy,but only were found in some podocytes of 2 females.The activity of α-Gal A was decreased compared with the normal range in 4 probands.The mutations of GLA were demonstrated in 11 patients.Three novel mutations of GLA gene were identified,which were all deletion/insertion mutations with classic phenotypes.Most variants carried the mutations located in the buried/partial buried areas of α-Gal A (3/11).The classical phenotype carried GLA mutations as W162X,F169S,S201F,N272K,L310R,while variant phenotype carried GLA mutations as I91T,R112H,Q312H.Conclusions The ratio of Fabry nephropathy in patients with renal biopsy is 0.074％.Angiokeratomas and cardiac involvement are often accompanied with Fabry nephropathy.The genotypes of GLA may have close relationships with the phenotypes of Fabry nephopathy.