Abstract: FR-PO620
Atypical Hemolytic Uremic Syndrome (HUS): DGKE and Other Mutations in West Virginia Children’s Hospital
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1600 Pediatric Nephrology
Authors
- Duvall, Kayla, WVU School of Medicine, Morgantown, West Virginia, United States
- Grossman, Oulimata K., West Virginia University Health Sciences, Morgantown, West Virginia, United States
Introduction
HUS is a thrombotic microangiopathy (TMA) presenting with thrombocytopenia, anemia, and end organ involvement with normal ADAMTS13. Microvascular injury, platelet consumption and intravascular hemolysis lead to end organ damage. Renal biopsy is pathognomonic. Typical HUS presents acutely after E. coli (STEC) related bloody diarrhea with good prognosis despite severity. Atypical HUS (aHUS) has incidence projected at 0.53 per million. Here we focus on etiologies related to complement dysregulation. AHUS is a chronic and progressive disease leading to acute kidney injury (AKI), end stage renal disease (ESRD), and even death. Early treatment with complement blockade (Eculizumab) has improved prognosis. Although a rare disease, this reports 3 cases managed in our institution to highlight the varied presentation and management.
Case Description
Patient A had TMA at 8 months old with proteinuria and progressed to ESRD at 19 years. Renal biopsy showed chronic TMA. This patient received Eculizumab for 4 months after renal transplant. Patient B was diagnosed at 3 years old with acute gastroenteritis, neurologic symptoms, and nephrotic syndrome. Renal biopsy showed acute TMA. Symptoms resolved with Eculizumab. Patient C presented at 10 years old with abdominal pain, gross hematuria, and proteinuria. Renal biopsy showed IgA nephropathy and no TMA lesions. This patient improved without Eculizumab.
Discussion
Despite similarities in presentation, it is vital to differentiate aHUS from HUS as early treatment with Eculizumab is recommended in aHUS to prevent morbidity. Genetics will determine who benefits from this treatment. Mutation in CFH gene is a major cause in up to 25% of cases, has poor prognosis, and requires plasma treatment. Patient B had such treatment and did have a secondary mutation on CFH compared to patient C who did not require treatment. MCP mutations are generally known to be associated with glomerulopathies and have better prognosis. DGKE, a rarely reported mutation, presents in infancy with ESRD by age 20 years and is not known to respond to Eculizumab without a secondary mutation. Extending our review on prior and future cases will give more insight to this very rare disease.
Genetics of Cases
| Patient A | Patient B | Patient C | |
| Major genetic mutation for gene mutation on Membrane cofactor protein (MCP, Complement factors I, B, H, CFHR4-6, Thrombomodulin, Diacydiacylglycerol kinase epsilon (DGKE) | Homozygous nonsense DGKE mutation(c.966G>A, p. Trp322Stop)Exon6 | Heterozygous missense variant (c.1058C>T, p.Ala353Val) Exon 8 MCP/CD46. Homozygous polymorphism (IVS9-78 G>A) MCP intron | Heterozygous, missense variant (c.1058C>T, p. Ala353Val) Exon 8 MCP/CD46. Homozygous polymorphism (IVS9-78 G>A) MCP intron |
| Minor genetic mutation(s) | Heterozygous missense variant of PLG (c.112A>G, p.Lys38Glu) on Exon2, (c.1469G>A, p.ARg49 Gln) on Exon 12. Heterozygous MCP/CD46 | Heterozygous for CFH C>T polymorphism | Heterozygous missense variant (c.754G>A, p.Gly252Ser) CFB exon |