Membranoproliferative glomerulonephritis and renal microangiopathies may manifest similar clinical presentations and histology. Many genetic mutations that cause these diseases have been reported. Studies on mutations in the gene encoding
diacylglycerol kinase epsilon identified a novel pathophysiologic mechanism leading to
atypical hemolytic uremic syndrome and/or
membranoproliferative glomerulonephritis. Here, we present the different clinical presentations and treatments in 4 family members who carried the same homozygous
diacylglycerol kinase epsilon mutation. The first patient (age 5 years, 3 months old at diagnosis) had
nephrotic syndrome. The kidney biopsy was
membranoproliferative glomerulonephritis; partial remission was achieved with
cyclophosphamide,
cyclosporine, and
mycophenolate mofetil treatment. The second patient (age 5 years, 7 months at diagnosis) presented with overlapping
atypical hemolytic uremic syndrome and
membranoproliferative glomerulonephritis. Remission could not be achieved with
cyclophosphamide,
cyclosporine, and
mycophenolate mofetil, and
hemodialysis treatment was started.
At 10 years from first admission, the patient had
end-stage kidney disease, and kidney transplant was performed successfully. The third patient was admitted with the diagnosis of
nephrotic syndrome at 13 months of age, kidney biopsy showed
membranoproliferative glomerulonephritis, and spontaneous remission developed during followup. He presented with
hemolytic uremic syndrome 15 months after the first admission, and dialysis was started. Remission was achieved with plasma infusion and
eculizumab treatment. The fourth patient (
a 7-month-old boy and brother of patient 3) had no clinical or laboratory findings. All patients had genetic analysis, and mutation in exon 2:c.473G>A(p. W158*) was detected. Our related patients with the same mutation showed different clinical and histological findings. However, we did not observe a clear genotype-phenotype correlation in patients with
diacylglycerol kinase epsilon nephropathy, suggesting additional factors mediating phenotypic heterogeneity.