The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase ε

被引:41
作者
Azukaitis, Karolis [1 ]
Simkova, Eva [2 ]
Majid, Mohammad Abdul [2 ]
Galiano, Matthias [3 ]
Benz, Kerstin [3 ]
Amann, Kerstin [4 ]
Bocknneyer, Clemens [4 ]
Gajjar, Radha [5 ]
Meyers, Kevin E. [5 ]
Cheong, Hae Ii [6 ,7 ]
Lange-Sperandio, Baerbel [8 ]
Jungraithnnayr, Therese [9 ]
Fremeaux-Bacchi, Veronique [10 ,11 ]
Bergmann, Carsten [12 ]
Bereczki, Csaba [13 ]
Miklaszewska, Monika [14 ]
Csuka, Dorottya [15 ]
Prohaszka, Zoltan [16 ]
Gipson, Patrick [17 ]
Sampson, Matthew G. [17 ]
Lennaire, Mathieu [18 ,19 ,20 ]
Schaefer, Franz [21 ]
机构
[1] Vilnius Univ, Clin Pediat, Fac Med, Santariskiu Str 4, LT-08661 Vilnius, Lithuania
[2] Dubai Hosp, Pediat Nephrol Dept, Dubai, U Arab Emirates
[3] Friedrich Alexander Univ Erlangen Nurnberg, Inst Pathol, Dept Pediat & Adolescent Med, Erlangen, Germany
[4] Friedrich Alexander Univ Erlangen Nurnberg, Inst Pathol, Dept Nephropathol, Erlangen, Germany
[5] Childrens Hosp Philadelphia, Dept Pediat, Div Nephrol, Philadelphia, PA 19104 USA
[6] Seoul Natl Univ, Childrens Hosp, Dept Paediat, Seoul, South Korea
[7] Seoul Natl Univ Hosp, Res Coordinat Ctr Rare Dis, Seoul, South Korea
[8] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Dept Pediat, Div Pediat Nephrol, Munich, Germany
[9] Klinikum Memmingen, Pediat Nephrol Ctr, Memmingen, Germany
[10] Hop Europeen Georges Pompidou, AP HP, Dept Immunol, Paris, France
[11] Ctr Rech Cordeliers, Unite Mixte Rech Sante 872, Paris, France
[12] Bioscientia, Ctr Human Genet, Ingelheim, Germany
[13] Univ Szeged, Dept Pediat, Szeged, Hungary
[14] Jagiellonian Univ, Med Coll, Dept Pediat Nephrol, Krakow, Poland
[15] Semmelweis Univ, Res Lab, Dept Internal Med 3, Budapest, Hungary
[16] Semmelweis Univ, George Fust Complement Diagnost Lab, Budapest, Hungary
[17] Univ Michigan, Sch Med, Dept Pediat, Nephrol Div, Ann Arbor, MI USA
[18] Hosp Sick Children, Res Inst, Program Cell Biol, Toronto, ON, Canada
[19] Univ Toronto, Dept Biochem, Fac Med, Toronto, ON, Canada
[20] Hosp Sick Children, Dept Paediat, Div Nephrol, Toronto, ON, Canada
[21] Heidelberg Univ, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2017年 / 28卷 / 10期
关键词
HEMOLYTIC-UREMIC SYNDROME; VARIANTS; SEQUENCE;
D O I
10.1681/ASN.2017010031
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
The recent discovery of mutations in the gene encoding diacylglycerol kinase epsilon (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.
引用
收藏
页码:3066 / 3075
页数:10
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