Year: 2026
Type: article
Study design: Case Report
Abstract: Complement dysregulation is frequently implicated in the thrombotic microangiopathy (TMA) known as atypical hemolytic uremic syndrome (aHUS). Diacylglycerol kinase epsilon (DGKE) mutations encode a non-complement regulatory protein, and pathogenic variants in DGKE define a distinct form of aHUS. Indeed, the DGKEgene encodes a key enzyme involved in intracellular signaling. While eculizumab and other anti-C5 monoclonal antibodies are widely used in complement-related aHUS, their relevance in DGKE-associated forms remains controversial. We report a case of a patient followed from the age of eight months for suspected aHUS. Genetic testing, performed only at the age of 13 years, revealed a homozygous DGKE mutation (c.412T>C; p.C138R), despite a typical presentation, including hemolytic anemia, thrombocytopenia, and acute kidney injury. Due to severe disease progression and a fatal family history, empirical eculizumab therapy was initiated. Although the treatment resulted in a stable overall clinical status, relapses manifested as isolated nephrotic-range proteinuria (without hemolysis) on two occasions during treatment interruptions. Complement C3 levels remained consistently within the normal range. In this case, eculizumab did not prevent disease relapses, which occurred in the absence of complement activation. The persistence of proteinuria despite C5 blockade further highlights this distinction. The lack of genetic testing options has led to overtreatment in this patient with that type of mutation, with additional costs associated with the drug (eculizumab) and an increased risk of life-threatening infectious complications for the patient.
Source: Cureus
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7147458595