U.S. Department of Health and Human Services

Mutations May Lead to Both Kidney and Blood Diseases

​A recently discovered set of gene mutations may be behind some cases of the serious blood disorder hemolytic uremic syndrome (HUS).

Hemolytic uremic syndrome is a condition that results from the premature destruction of red blood cells. These red blood cell fragments can clog the kidneys’ iltering system and cause kidney failure. While many cases of HUS result from a bacterial infection, so-called atypical HUS (aHUS) arises from genetic or autoimmune factors. Researchers have now identiied a set of novel mutations in the gene for diacylglycerol kinase epsilon (DGKE) that is associated with aHUS in nine unrelated families. The protein encoded by the DGKE gene is found in several cell types, including the blood vessels and iltering cells of the human kidney; thus, its disruption has the potential to have wide-ranging effects throughout the body.

People with the mutated DGKE genes typically develop aHUS before one year of age, have persistent high blood pressure, blood and protein in their urine, and are likely to develop chronic kidney disease as they age. The DGKE mutations identiied in all nine families seemed to produce a non-functional, sometimes truncated DGKE protein, suggesting that the loss of DGKE function within cells might be responsible for these cases of aHUS. These indings implicate loss of DKGE function as a cause of a distinct subset of aHUS cases that may lead to severe kidney complications not usually seen in other forms of aHUS.

DGKE is the irst gene implicated in aHUS that is not part of the complement system, a blood-borne part of the immune system. Currently, patients with aHUS are usually treated with drugs that inhibit the complement system, but this approach may be ineffective in people with DGKE mutations. For these individuals, kidney transplantation may represent a more effective treatment. These indings underscore the importance of correctly diagnosing patients whose aHUS arises from DKGE mutations and tailoring their treatment accordingly.

Lemaire M, Frémeaux-Bacchi V, Schaefer F, et al. Recessive
mutations in DGKE cause atypical hemolytic-uremic
syndrome. Nature Genet 45: 531-536, 2013.