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.