A Novel Missense GLA Mutation (p.G35V) Detected in Hemodialysis Screening Leads to Severe Systemic Manifestations of Fabry Disease in Men and Women

被引：14

作者：

Pigozzi Veloso, Valeria Soares ^{[1
]}

Ataides, Thiago Lacerda ^{[1
]}

Fernandes Canziani, Maria Eugenia ^{[2
]}

Veloso, Mariana Pigozzi ^{[1
]}

da Silva, Nilzio Antonio ^{[1
]}

Barreto, Daniela Veit ^{[4
]}

Silva Pereira, Edna Regina ^{[1
]}

Ribeiro de Moura, Luiz Antonio ^{[2
,3
]}

Barreto, Fellype Carvalho ^{[5
]}

机构：

[1] Univ Fed Goias, Dept Internal Med, Goiania, Go, Brazil

[2] Univ Fed Sao Paulo, Div Nephrol, Dept Internal Med, Sao Paulo, Brazil

[3] Hosp Rim & Hipertensao, Renal Pathol Lab, Sao Paulo, Brazil

[4] Hosp Marcelino Champagnat, Serv Internal Med, Curitiba, Parana, Brazil

[5] Univ Fed Parana, Div Nephrol, Dept Internal Med, Curitiba, Parana, Brazil

来源：

NEPHRON | 2018年 / 138卷 / 02期

关键词：

Fabry's disease; Kidney biopsy; Podocyte; Genetic diseases; Kidney histology; Anderson-Fabry disease; Interstitial fibrosis; Glomerulus; Hemodialysis; FOOT PROCESS EFFACEMENT; CLINICAL-SIGNIFICANCE; ALPHA-GALACTOSIDASE; FEMALE-PATIENTS; SCORING SYSTEM; ADULT PATIENTS; NEPHROPATHY; PREVALENCE; ALBUMINURIA; PODOCYTURIA;

D O I：

10.1159/000479895

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background/Aims: Fabry disease (FD), an X-linked lysosomal storage disorder, leads to accumulation of globotriaosylceramide. Screening in dialysis patients may identify genetic variants of unknown clinical significance. We aimed to characterize the pathogenicity of a novel GLA gene mutation identified during hemodialysis screening and the histologic findings of early Fabry nephropathy. Methods: One out of 108 male hemodialysis patients screened for FD presented low alpha-galactosidase A activity. A novel missense mutation (p.G35V) in the GLA gene was detected. Family screening identified 11 additional cases (8 women). Clinical investigation was conducted in 10 patients (index case and 9 relatives). Pathogenicity of the new mutation was investigated by clinical and laboratory tests, cardiac and cranial magnetic resonance imaging, and kidney biopsy. Results: Cardiac manifestations were detected in most patient from both genders, such as left ventricular hypertrophy and short PR interval. White matter lesion was present in 3 women. Pulvinar lesion of the thalamus and ischemic stroke were detected in male patients. Abnormal glomerular filtration rate (GFR) and/or albuminuria were present in 5 patients (3 women). Renal biopsies (n = 7) revealed globotriaosylceramide deposits in different cell types and foot processes effacement in all patients, including women with normal albuminuria. Despite a normal GFR, tubulointerstitial fibrosis ranging from 5 to 20% was present in young women and men with normal or high albuminuria, respectively. Conclusion: The novel missense mutation p.G35V leads to severe systemic manifestations of FD in men and women. Kidney histological changes, including tubulointerstitial fibrosis, may predate albuminuria and GFR changes in adult women. Novel non-invasive markers are required for early detection of Fabry nephropathy. (C) 2017 S. Karger AG, Basel

引用

页码：147 / 156

页数：10