BackgroundAtypical 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 ofDGKE-aHUS patients have not yet been fully elucidated. The aim of this study was to report a novel variant of theDGKEgene in a Chinese population with aHUS.Case presentationThe 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 theDGKEexon region: NM_003647.2, c.610dup, p.Thr204Asnfs*4 and deletion of exons 4–6.ConclusionsThis case suggest that atypical HUS withDGKEgene 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 forDGKE-aHUS. There have an uncertain benefit of plasma therapy forDGKE-aHUS patients. The literature demonstrated that anti-complement therapy showed benefits forDGKE-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.