Clinical features and management of atypical hemolytic uremic syndrome patient with DGKE gene variants: a case report

Xiaomei Dai; Yu Ma; Qiang Lin; Hanyun Tang; Ruyue Chen; Yun Zhu; Yunyan Shen; Ningxun Cui; Zhongqin Hong; Yanhong Li; Xiaozhong Li

doi:10.3389/fped.2023.1162974

Clinical features and management of atypical hemolytic uremic syndrome patient with DGKE gene variants: a case report

Front Pediatr. 2023 Jun 29:11:1162974. doi: 10.3389/fped.2023.1162974. eCollection 2023.

Authors

Xiaomei Dai^#¹, Yu Ma^#², Qiang Lin¹, Hanyun Tang¹, Ruyue Chen¹, Yun Zhu¹, Yunyan Shen¹, Ningxun Cui¹, Zhongqin Hong¹, Yanhong Li^{1

3}, Xiaozhong Li¹

Affiliations

¹ Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, China.
² Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou, China.
³ Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.

^# Contributed equally.

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) with diacylglycerol kinase epsilon (DGKE) gene variant is a rare variant of thrombotic microangiopathy (TMA). The information on the clinical features, management and long-term outcomes of DGKE-aHUS patients have not yet been fully elucidated. The aim of this study was to report a novel variant of the DGKE gene in a Chinese population with aHUS.

Case presentation: The present work reports a 7-month-old boy with aHUS, possibly triggered by gastrointestinal infection, without complement activation, with little response to plasma therapy and nephroprotective measures. The patient died during the 8th week of his hospital stay. The causes of death were intracranial hemorrhage and multiorgan dysfunction. Comprehensive WES of peripheral blood-derived DNA revealed two heterozygous variations in the DGKE exon region: NM_003647.2, c.610dup, p.Thr204Asnfs*4 and deletion of exons 4-6.

Conclusions: This case suggest that atypical HUS with DGKE gene variant has a poor prognosis with a high mortality rate, which typically manifests in the first year of life and presents as a systemic disease with early-onset HUS with rapidly worsening renal function and chronic proteinuria. There is no specific treatment for DGKE-aHUS. There have an uncertain benefit of plasma therapy for DGKE-aHUS patients. The literature demonstrated that anti-complement therapy showed benefits for DGKE-aHUS with complement activation and autoantibodies during the overt TMA presentation but did not prevent TMA relapses. Early diagnosis and treatment may prevent complications and improve prognosis.

Keywords: DGKE gene; TMA; atypical hemolytic uremic syndrome; chronic kidney disease (CKD); plasma therapy.

Publication types

Review

Grants and funding

This work was supported by grants from the Science and Technology Development Project of Suzhou City (SS202067) and Key Discipline of Pediatric Immunology (SZXK202106). The funders had no role in study design, data collection, preparation of the manuscript, and decision to publish.